Wiley Interdisciplinary Reviews: Computational Molecular Science最新文献_第6页

Revolutionizing peptide-based drug discovery: Advances in the post-AlphaFold era 肽类药物发现的革命性变革：后阿尔法折叠时代的进步

IF 11.4 2区化学

Wiley Interdisciplinary Reviews: Computational Molecular Science Pub Date : 2023-11-12 DOI: 10.1002/wcms.1693

Liwei Chang, Arup Mondal, Bhumika Singh, Yisel Martínez-Noa, Alberto Perez

{"title":"Revolutionizing peptide-based drug discovery: Advances in the post-AlphaFold era","authors":"Liwei Chang, Arup Mondal, Bhumika Singh, Yisel Martínez-Noa, Alberto Perez","doi":"10.1002/wcms.1693","DOIUrl":"10.1002/wcms.1693","url":null,"abstract":"Peptide-based drugs offer high specificity, potency, and selectivity. However, their inherent flexibility and differences in conformational preferences between their free and bound states create unique challenges that have hindered progress in effective drug discovery pipelines. The emergence of AlphaFold (AF) and Artificial Intelligence (AI) presents new opportunities for enhancing peptide-based drug discovery. We explore recent advancements that facilitate a successful peptide drug discovery pipeline, considering peptides' attractive therapeutic properties and strategies to enhance their stability and bioavailability. AF enables efficient and accurate prediction of peptide-protein structures, addressing a critical requirement in computational drug discovery pipelines. In the post-AF era, we are witnessing rapid progress with the potential to revolutionize peptide-based drug discovery such as the ability to rank peptide binders or classify them as binders/non-binders and the ability to design novel peptide sequences. However, AI-based methods are struggling due to the lack of well-curated datasets, for example to accommodate modified amino acids or unconventional cyclization. Thus, physics-based methods, such as docking or molecular dynamics simulations, continue to hold a complementary role in peptide drug discovery pipelines. Moreover, MD-based tools offer valuable insights into binding mechanisms, as well as the thermodynamic and kinetic properties of complexes. As we navigate this evolving landscape, a synergistic integration of AI and physics-based methods holds the promise of reshaping the landscape of peptide-based drug discovery.This article is categorized under:\u0000 ","PeriodicalId":236,"journal":{"name":"Wiley Interdisciplinary Reviews: Computational Molecular Science","volume":"14 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2023-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135036898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Simplified quantum chemistry methods to evaluate non-linear optical properties of large systems 评估大型系统非线性光学特性的简化量子化学方法

IF 11.4 2区化学

Wiley Interdisciplinary Reviews: Computational Molecular Science Pub Date : 2023-11-05 DOI: 10.1002/wcms.1695

Sarah Löffelsender, Pierre Beaujean, Marc de Wergifosse

{"title":"Simplified quantum chemistry methods to evaluate non-linear optical properties of large systems","authors":"Sarah Löffelsender, Pierre Beaujean, Marc de Wergifosse","doi":"10.1002/wcms.1695","DOIUrl":"10.1002/wcms.1695","url":null,"abstract":"This review presents the theoretical background concerning simplified quantum chemistry (sQC) methods to compute non-linear optical (NLO) properties and their applications to large systems. To evaluate any NLO responses such as hyperpolarizabilities or two-photon absorption (2PA), one should evidently perform first a ground state calculation and compute its response. Because of this, methods used to compute ground states of large systems are outlined, especially the xTB (extended tight-binding) scheme. An overview on approaches to compute excited state and response properties is given, emphasizing the simplified time-dependent density functional theory (sTD-DFT). The formalism of the eXact integral sTD-DFT (XsTD-DFT) method is also introduced. For the first hyperpolarizability, 2PA, excited state absorption, and second hyperpolarizability, a brief historical review is given on early-stage semi-empirical method applications to systems that were considered large at the time. Then, we showcase recent applications with sQC methods, especially the sTD-DFT scheme to large challenging systems such as fluorescent proteins or fluorescent organic nanoparticles as well as dynamic structural effects on flexible tryptophan-rich peptides and gramicidin A. Thanks to the sTD-DFT-xTB scheme, all-atom quantum chemistry methodologies are now possible for the computation of the first hyperpolarizability and 2PA of systems up to 5000 atoms. This review concludes by summing-up current and future method developments in the sQC framework as well as forthcoming applications on large systems.This article is categorized under:\u0000 ","PeriodicalId":236,"journal":{"name":"Wiley Interdisciplinary Reviews: Computational Molecular Science","volume":"14 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2023-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135726599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Molecular simulation approaches to study crystal nucleation from solutions: Theoretical considerations and computational challenges 研究溶液晶体成核的分子模拟方法：理论考虑和计算挑战

IF 11.4 2区化学

Wiley Interdisciplinary Reviews: Computational Molecular Science Pub Date : 2023-11-01 DOI: 10.1002/wcms.1697

Aaron R. Finney, Matteo Salvalaglio

{"title":"Molecular simulation approaches to study crystal nucleation from solutions: Theoretical considerations and computational challenges","authors":"Aaron R. Finney, Matteo Salvalaglio","doi":"10.1002/wcms.1697","DOIUrl":"10.1002/wcms.1697","url":null,"abstract":"Nucleation is the initial step in the formation of crystalline materials from solutions. Various factors, such as environmental conditions, composition, and external fields, can influence its outcomes and rates. Indeed, controlling this rate-determining step toward phase separation is critical, as it can significantly impact the resulting material's structure and properties. Atomistic simulations can be exploited to gain insight into nucleation mechanisms—an aspect difficult to ascertain in experiments—and estimate nucleation rates. However, the microscopic nature of simulations can influence the phase behavior of nucleating solutions when compared to macroscale counterparts. An additional challenge arises from the inadequate timescales accessible to standard molecular simulations to simulate nucleation directly; this is due to the inherent rareness of nucleation events, which may be apparent in silico at even high supersaturations. In recent decades, molecular simulation methods have emerged to circumvent length- and timescale limitations. However, it is not always clear which simulation method is most suitable to study crystal nucleation from solution. This review surveys recent advances in this field, shedding light on typical nucleation mechanisms and the appropriateness of various simulation techniques for their study. Our goal is to provide a deeper understanding of the complexities associated with modeling crystal nucleation from solution and identify areas for further research. This review targets researchers across various scientific domains, including materials science, chemistry, physics and engineering, and aims to foster collaborative efforts to develop new strategies to understand and control nucleation.This article is categorized under:\u0000 ","PeriodicalId":236,"journal":{"name":"Wiley Interdisciplinary Reviews: Computational Molecular Science","volume":"14 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/wcms.1697","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135272408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The versatility of the Cholesky decomposition in electronic structure theory 乔利斯基分解在电子结构理论中的多功能性

IF 11.4 2区化学

Wiley Interdisciplinary Reviews: Computational Molecular Science Pub Date : 2023-10-25 DOI: 10.1002/wcms.1692

Thomas Bondo Pedersen, Susi Lehtola, Ignacio Fdez. Galván, Roland Lindh

{"title":"The versatility of the Cholesky decomposition in electronic structure theory","authors":"Thomas Bondo Pedersen, Susi Lehtola, Ignacio Fdez. Galván, Roland Lindh","doi":"10.1002/wcms.1692","DOIUrl":"10.1002/wcms.1692","url":null,"abstract":"The resolution-of-the-identity (RI) or density fitting (DF) approximation for the electron repulsion integrals (ERIs) has become a standard component of accelerated and reduced-scaling implementations of first-principles Gaussian-type orbital electronic-structure methods. The Cholesky decomposition (CD) of the ERIs has also become increasingly deployed across quantum chemistry packages in the last decade, even though its early applications were mostly limited to high-accuracy methods such as coupled-cluster theory and multiconfigurational approaches. Starting with a summary of the basic theory underpinning both the CD and RI/DF approximations, thus underlining the extremely close relation of the CD and RI/DF techniques, we provide a brief and largely chronological review of the evolution of the CD approach from its birth in 1977 to its current state. In addition to being a purely numerical procedure for handling ERIs, thus providing robust and computationally efficient approximations to the exact ERIs that have been found increasingly useful on modern computer platforms, CD also offers highly accurate approaches for generating auxiliary basis sets for the RI/DF approximation on the fly due to the deep mathematical connection between the two approaches. In this review, we aim to provide a concise reference of the main techniques employed in various CD approaches in electronic structure theory, to exemplify the connection between the CD and RI/DF approaches, and to clarify the state of the art to guide new implementations of CD approaches across electronic structure programs.This article is categorized under:\u0000 ","PeriodicalId":236,"journal":{"name":"Wiley Interdisciplinary Reviews: Computational Molecular Science","volume":"14 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2023-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/wcms.1692","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135215975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Recent advances in deep learning for retrosynthesis 逆合成深度学习的最新进展

IF 11.4 2区化学

Wiley Interdisciplinary Reviews: Computational Molecular Science Pub Date : 2023-10-20 DOI: 10.1002/wcms.1694

Zipeng Zhong, Jie Song, Zunlei Feng, Tiantao Liu, Lingxiang Jia, Shaolun Yao, Tingjun Hou, Mingli Song

{"title":"Recent advances in deep learning for retrosynthesis","authors":"Zipeng Zhong, Jie Song, Zunlei Feng, Tiantao Liu, Lingxiang Jia, Shaolun Yao, Tingjun Hou, Mingli Song","doi":"10.1002/wcms.1694","DOIUrl":"10.1002/wcms.1694","url":null,"abstract":"Retrosynthesis is the cornerstone of organic chemistry, providing chemists in material and drug manufacturing access to poorly available and brand-new molecules. Conventional rule-based or expert-based computer-aided synthesis has obvious limitations, such as high labor costs and limited search space. In recent years, dramatic breakthroughs driven by deep learning have revolutionized retrosynthesis. Here we aim to present a comprehensive review of recent advances in AI-based retrosynthesis. For single-step and multi-step retrosynthesis both, we first introduce their goal and provide a thorough taxonomy of existing methods. Afterwards, we analyze these methods in terms of their mechanism and performance, and introduce popular evaluation metrics for them, in which we also provide a detailed comparison among representative methods on several public datasets. In the next part, we introduce popular databases and established platforms for retrosynthesis. Finally, this review concludes with a discussion about promising research directions in this field.This article is categorized under:\u0000 ","PeriodicalId":236,"journal":{"name":"Wiley Interdisciplinary Reviews: Computational Molecular Science","volume":"14 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2023-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135570895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The kth nearest neighbor method for estimation of entropy changes from molecular ensembles 估计分子集合熵变化的第 k 次近邻法

IF 11.4 2区化学

Wiley Interdisciplinary Reviews: Computational Molecular Science Pub Date : 2023-10-02 DOI: 10.1002/wcms.1691

Federico Fogolari, Roberto Borelli, Agostino Dovier, Gennaro Esposito

{"title":"The kth nearest neighbor method for estimation of entropy changes from molecular ensembles","authors":"Federico Fogolari, Roberto Borelli, Agostino Dovier, Gennaro Esposito","doi":"10.1002/wcms.1691","DOIUrl":"10.1002/wcms.1691","url":null,"abstract":"All processes involving molecular systems entail a balance between associated enthalpic and entropic changes. Molecular dynamics simulations of the end-points of a process provide in a straightforward way the enthalpy as an ensemble average. Obtaining absolute entropies is still an open problem and most commonly pathway methods are used to obtain free energy changes and thereafter entropy changes. The kth nearest neighbor (kNN) method has been first proposed as a general method for entropy estimation in the mathematical community 20 years ago. Later, it has been applied to compute conformational, positional–orientational, and hydration entropies of molecules. Programs to compute entropies from molecular ensembles, for example, from molecular dynamics (MD) trajectories, based on the kNN method, are currently available. The kNN method has distinct advantages over traditional methods, namely that it is possible to address high-dimensional spaces, impossible to treat without loss of resolution or drastic approximations with, for example, histogram-based methods. Application of the method requires understanding the features of: the kth nearest neighbor method for entropy estimation; the variables relevant to biomolecular and in general molecular processes; the metrics associated with such variables; the practical implementation of the method, including requirements and limitations intrinsic to the method; and the applications for conformational, position/orientation and solvation entropy. Coupling the method with general approximations for the multivariable entropy based on mutual information, it is possible to address high dimensional problems like those involving the conformation of proteins, nucleic acids, binding of molecules and hydration.This article is categorized under:\u0000 ","PeriodicalId":236,"journal":{"name":"Wiley Interdisciplinary Reviews: Computational Molecular Science","volume":"14 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2023-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/wcms.1691","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135792985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Polaritonic response theory for exact and approximate wave functions 精确和近似波函数的极性响应理论

IF 11.4 2区化学

Wiley Interdisciplinary Reviews: Computational Molecular Science Pub Date : 2023-10-01 DOI: 10.1002/wcms.1684

Matteo Castagnola, Rosario Roberto Riso, Alberto Barlini, Enrico Ronca, Henrik Koch

{"title":"Polaritonic response theory for exact and approximate wave functions","authors":"Matteo Castagnola, Rosario Roberto Riso, Alberto Barlini, Enrico Ronca, Henrik Koch","doi":"10.1002/wcms.1684","DOIUrl":"10.1002/wcms.1684","url":null,"abstract":"Polaritonic chemistry is an interdisciplinary emerging field that presents several challenges and opportunities in chemistry, physics, and engineering. A systematic review of polaritonic response theory is presented, following a chemical perspective based on molecular response theory. We provide the reader with a general strategy for developing response theory for ab initio cavity quantum electrodynamics (QED) methods and critically emphasize details that still need clarification and require cooperation between the physical and chemistry communities. We show that several well-established results can be applied to strong coupling light-matter systems, leading to novel perspectives on the computation of matter and photonic properties. The application of the Pauli–Fierz Hamiltonian to polaritons is discussed, focusing on the effects of describing operators in different mathematical representations. We thoroughly examine the most common approximations employed in ab initio QED, such as the dipole approximation. We introduce the polaritonic response equations for the recently developed ab initio QED Hartree–Fock and QED coupled cluster methods. The discussion focuses on the similarities and differences from standard quantum chemistry methods, providing practical equations for computing the polaritonic properties.This article is categorized under:\u0000 ","PeriodicalId":236,"journal":{"name":"Wiley Interdisciplinary Reviews: Computational Molecular Science","volume":"14 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/wcms.1684","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135458261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ring kinematics-informed conformation space exploration 基于环运动学的构象空间探索

IF 11.4 2区化学

Wiley Interdisciplinary Reviews: Computational Molecular Science Pub Date : 2023-09-26 DOI: 10.1002/wcms.1690

Nikolai V. Krivoshchapov, Michael G. Medvedev

{"title":"Ring kinematics-informed conformation space exploration","authors":"Nikolai V. Krivoshchapov, Michael G. Medvedev","doi":"10.1002/wcms.1690","DOIUrl":"10.1002/wcms.1690","url":null,"abstract":"Conformational searches and ML-driven geometry predictions (e.g., AlphaFold) work in the space of molecule's degrees of freedom. When dealing with cycles, cyclicity constraints impose complex interdependence between them, so that arbitrary changes of cyclic dihedral angles lead to heavy distortions of some bond lengths and valence angles of the ring. This renders navigation through conformational space of cyclic molecules to be very challenging. Inverse kinematics is a theory that provides a mathematically strict solution to this problem. It allows one to identify degrees of freedom for any polycyclic molecule, that is, its dihedral angles that can be set independently from each other. Then for any values of degrees of freedom, inverse kinematics can reconstruct the remaining dihedrals so that all rings are closed with given bond lengths and valence angles. This approach offers a handy and efficient way for constructing and navigating conformational space of any molecule using either naïve Monte-Carlo sampling or sophisticated machine learning models. Inverse kinematics can considerably narrow the conformational space of a polycyclic molecule to include only cyclicity-preserving regions. Thus, it can be viewed as a physical constraint on the model, making the latter obey the laws of kinematics, which govern the rings conformations. We believe that inverse kinematics will be universally used in the ever-growing field of geometry prediction of complex interlinked molecules.This article is categorized under:\u0000 ","PeriodicalId":236,"journal":{"name":"Wiley Interdisciplinary Reviews: Computational Molecular Science","volume":"14 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2023-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134885941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Computational biophysics meets cryo-EM revolution in the search for the functional dynamics of biomolecular systems 计算生物物理学与低温电子显微镜革命在探索生物分子系统功能动态中的结合

IF 11.4 2区化学

Wiley Interdisciplinary Reviews: Computational Molecular Science Pub Date : 2023-09-21 DOI: 10.1002/wcms.1689

Mauricio G. S. Costa, Mert Gur, James M. Krieger, Ivet Bahar

{"title":"Computational biophysics meets cryo-EM revolution in the search for the functional dynamics of biomolecular systems","authors":"Mauricio G. S. Costa, Mert Gur, James M. Krieger, Ivet Bahar","doi":"10.1002/wcms.1689","DOIUrl":"10.1002/wcms.1689","url":null,"abstract":"There is a variety of experimental and computational techniques available to explore protein dynamics, each presenting advantages and limitations. One promising experimental technique that is driving the development of computational methods is cryo-electron microscopy (cryo-EM). Cryo-EM provides molecular-level structural data and first estimates of conformational landscape from single particle analysis but cannot track real-time protein dynamics and may contain uncertainties in atomic positions especially at highly dynamic regions. Molecular simulations offer atomic-level insights into protein dynamics; however, their computing time requirements limit the conformational sampling accuracy, and it is often hard, to assess by full-atomic simulations the cooperative movements of biological interest for large assemblies such as those resolved by cryo-EM. Coarse-grained (CG) simulations permit us to explore such systems, but at the costs of lower resolution and potentially incomplete sampling of conformational space. On the other hand, analytical methods may circumvent sampling limitations. In particular, elastic network models-based normal mode analyses (ENM-NMA) provide unique solutions for the complete mode spectra near equilibrium states, even for systems of megadaltons, and may thus deliver information on mechanisms of motions relevant to biological function. Yet, they lack atomic resolution as well as temporal information for non-equilibrium systems. Given the complementary nature of these methods, the integration of molecular simulations and ENM-NMA into hybrid methodologies has gained traction. This review presents the current state-of-the-art in structure-based computations and how they are helping us gain a deeper understanding of biological mechanisms, with emphasis on the development of hybrid methods accompanying the advances in cryo-EM.This article is categorized under:\u0000 ","PeriodicalId":236,"journal":{"name":"Wiley Interdisciplinary Reviews: Computational Molecular Science","volume":"14 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2023-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/wcms.1689","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136129851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cover Image, Volume 13, Issue 5 封面图片，第13卷第5期

IF 11.4 2区化学

Wiley Interdisciplinary Reviews: Computational Molecular Science Pub Date : 2023-09-21 DOI: 10.1002/wcms.1688

Juan V. Alegre-Requena, Shree Sowndarya S. V., Raúl Pérez-Soto, Turki M. Alturaifi, Robert S. Paton

引用次数: 0