文献检索文档翻译深度研究
Suppr Zotero 插件Zotero 插件
邀请有礼套餐&价格历史记录

新学期,新优惠

限时优惠:9月1日-9月22日

30天高级会员仅需29元

1天体验卡首发特惠仅需5.99元

了解详情
不再提醒
插件&应用
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
高级版
套餐订阅购买积分包
AI 工具
文献检索文档翻译深度研究
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利:CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2025

发展和全面基准测试具有广泛化学空间覆盖的高质量 AMBER 一致性小分子力场,用于分子建模和自由能计算。

Development and Comprehensive Benchmark of a High-Quality AMBER-Consistent Small Molecule Force Field with Broad Chemical Space Coverage for Molecular Modeling and Free Energy Calculation.

机构信息

Shenzhen Jingtai Technology Co., Ltd. (XtalPi), Floor 3, Sf Industrial Plant, No. 2 Hongliu Road, Fubao Community, Fubao Street, Futian District, Shenzhen 518045, China.

Medicine Design, Pfizer Inc., 1 Portland Street, Cambridge, Massachusetts 02139, United States.

出版信息

J Chem Theory Comput. 2024 Jan 23;20(2):799-818. doi: 10.1021/acs.jctc.3c00920. Epub 2023 Dec 29.


DOI:10.1021/acs.jctc.3c00920
PMID:38157475
Abstract

Biomolecular simulations have become an essential tool in contemporary drug discovery, and molecular mechanics force fields (FFs) constitute its cornerstone. Developing a high quality and broad coverage general FF is a significant undertaking that requires substantial expert knowledge and computing resources, which is beyond the scope of general practitioners. Existing FFs originate from only a limited number of groups and organizations, and they either suffer from limited numbers of training sets, lower than desired quality because of oversimplified representations, or are costly for the molecular modeling community to access. To address these issues, in this work, we developed an AMBER-consistent small molecule FF with extensive chemical space coverage, and we provide Open Access parameters for the entire modeling community. To validate our FF, we carried out benchmarks of quantum mechanics (QM)/molecular mechanics conformer comparison and free energy perturbation calculations on several benchmark data sets. Our FF achieves a higher level of performance at reproducing QM energies and geometries than two popular open-source FFs, OpenFF2 and GAFF2. In relative binding free energy calculations for 31 protein-ligand data sets, comprising 1079 pairs of ligands, the new FF achieves an overall root-mean-square error of 1.19 kcal/mol for ΔΔ and 0.92 kcal/mol for Δ on a subset of 463 ligands without bespoke fitting to the data sets. The results are on par with those of the leading commercial series of OPLS FFs.

摘要

生物分子模拟已成为当代药物发现的重要工具,而分子力学力场 (FF) 则构成了其基石。开发高质量且广泛涵盖的通用 FF 是一项重大任务,需要大量的专业知识和计算资源,这超出了普通从业者的能力范围。现有的 FF 仅源于有限数量的小组和组织,它们要么受到训练集数量有限的限制,要么由于表示过于简化而导致质量不如预期,要么对分子建模社区来说访问成本过高。为了解决这些问题,在这项工作中,我们开发了一种具有广泛化学空间覆盖范围的与 AMBER 一致的小分子 FF,并为整个建模社区提供了开放访问参数。为了验证我们的 FF,我们对几个基准数据集进行了量子力学 (QM)/分子力学构象比较和自由能微扰计算的基准测试。与两个流行的开源 FF(OpenFF2 和 GAFF2)相比,我们的 FF 在再现 QM 能量和几何形状方面表现更为出色。在对包含 1079 对配体的 31 个蛋白-配体数据集进行相对结合自由能计算时,新的 FF 在没有对数据集进行专门拟合的情况下,对于 463 个配体子集,ΔΔ 的总体均方根误差为 1.19 kcal/mol,Δ 为 0.92 kcal/mol。其结果与领先的 OPLS FF 商业系列相当。

相似文献

[1]
Development and Comprehensive Benchmark of a High-Quality AMBER-Consistent Small Molecule Force Field with Broad Chemical Space Coverage for Molecular Modeling and Free Energy Calculation.

J Chem Theory Comput. 2024-1-23

[2]
Biomolecular force fields: where have we been, where are we now, where do we need to go and how do we get there?

J Comput Aided Mol Des. 2018-11-30

[3]
Practical Guidance for Consensus Scoring and Force Field Selection in Protein-Ligand Binding Free Energy Simulations.

J Chem Inf Model. 2022-12-12

[4]
CHARMM-GUI Free Energy Calculator for Practical Ligand Binding Free Energy Simulations with AMBER.

J Chem Inf Model. 2021-9-27

[5]
Benchmark assessment of molecular geometries and energies from small molecule force fields.

F1000Res. 2020

[6]
Force field development phase II: Relaxation of physics-based criteria… or inclusion of more rigorous physics into the representation of molecular energetics.

J Comput Aided Mol Des. 2018-11-30

[7]
Computation of Protein-Ligand Binding Free Energies with a Quantum Mechanics-Based Mining Minima Algorithm.

J Chem Theory Comput. 2025-4-22

[8]
Protein-Ligand Binding Free-Energy Calculations with ARROW─A Purely First-Principles Parameterized Polarizable Force Field.

J Chem Theory Comput. 2022-12-13

[9]
Can We Ever Develop an Ideal RNA Force Field? Lessons Learned from Simulations of the UUCG RNA Tetraloop and Other Systems.

J Chem Theory Comput. 2025-4-22

[10]
Prediction of hydration free energies for aliphatic and aromatic chloro derivatives using molecular dynamics simulations with the OPLS-AA force field.

J Comput Aided Mol Des. 2011-12-21

引用本文的文献

[1]
Validating Small-Molecule Force Fields for Macrocyclic Compounds Using NMR Data in Different Solvents.

J Chem Inf Model. 2024-10-28

[2]
The Open Force Field Initiative: Open Software and Open Science for Molecular Modeling.

J Phys Chem B. 2024-7-25

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

推荐工具

医学文档翻译智能文献检索