The MM/PBSA and MM/GBSA methods to estimate ligand-binding affinities
Samuel Genheden,Ulf Ryde +1 more
Reads0
Chats0
TLDR
The authors review the use of MM/PBSA and MM/GBSA methods to calculate ligand-binding affinities, with an emphasis on calibration, testing and validation, as well as attempts to improve the methods, rather than on specific applications.Abstract:
Introduction: The molecular mechanics energies combined with the Poisson–Boltzmann or generalized Born and surface area continuum solvation (MM/PBSA and MM/GBSA) methods are popular approaches to estimate the free energy of the binding of small ligands to biological macromolecules. They are typically based on molecular dynamics simulations of the receptor–ligand complex and are therefore intermediate in both accuracy and computational effort between empirical scoring and strict alchemical perturbation methods. They have been applied to a large number of systems with varying success.Areas covered: The authors review the use of MM/PBSA and MM/GBSA methods to calculate ligand-binding affinities, with an emphasis on calibration, testing and validation, as well as attempts to improve the methods, rather than on specific applications.Expert opinion: MM/PBSA and MM/GBSA are attractive approaches owing to their modular nature and that they do not require calculations on a training set. They have been used success...read more
Citations
More filters
Journal ArticleDOI
End-Point Binding Free Energy Calculation with MM/PBSA and MM/GBSA: Strategies and Applications in Drug Design
TL;DR: In this review, methods to adjust the polar solvation energy and to improve the performance of MM/PBSA and MM/GBSA calculations are reviewed and discussed and guidance is provided for practically applying these methods in drug design and related research fields.
Journal ArticleDOI
Insights into Protein-Ligand Interactions: Mechanisms, Models, and Methods
Xing Du,Yi Li,Yuan-Ling Xia,Shi-Meng Ai,Shi-Meng Ai,Jing Liang,Peng Sang,Peng Sang,Xing-Lai Ji,Shu-Qun Liu +9 more
TL;DR: The physicochemical mechanisms underlying protein–ligand binding, including the binding kinetics, thermodynamic concepts and relationships, and binding driving forces, are introduced and rationalized.
Journal ArticleDOI
Molecular Docking: Shifting Paradigms in Drug Discovery.
Luca Pinzi,Giulio Rastelli +1 more
TL;DR: This review describes how molecular docking was firstly applied to assist in drug discovery tasks, and illustrates newer and emergent uses and applications of docking, including prediction of adverse effects, polypharmacology, drug repurposing, and target fishing and profiling.
Journal ArticleDOI
Isolation of SARS-CoV-2-related coronavirus from Malayan pangolins.
Kangpeng Xiao,Junqiong Zhai,Yaoyu Feng,Niu Zhou,Xu Zhang,Jie Jian Zou,Na Li,Yaqiong Guo,Xiaobing Li,Shen Xuejuan,Zhipeng Zhang,Fanfan Shu,Wanyi Huang,Yu Li,Ziding Zhang,Rui Ai Chen,Ya Jiang Wu,Shi Ming Peng,Mian Huang,Wei-Jun Xie,Qin Hui Cai,Fang Hui Hou,Wu Chen,Lihua Xiao,Yongyi Shen +24 more
TL;DR: It is shown that a coronavirus isolated from a Malayan pangolin has 100%, 98.6%, 97.8% and 90.7% amino acid identity with SARS-CoV-2 in the E, M, N and S proteins, respectively, which suggests that the latter may have originated from a recombination event involving Sars-related coronaviruses from bats and pangolins.
Journal ArticleDOI
Relative Binding Free Energy Calculations in Drug Discovery: Recent Advances and Practical Considerations
TL;DR: An overview of current RBFE implementations, highlighting recent advances and remaining challenges, along with examples that emphasize practical considerations for obtaining reliable RBFE results is presented, with a focus on real-world drug discovery applications.
References
More filters
Journal ArticleDOI
Calculating Structures and Free Energies of Complex Molecules: Combining Molecular Mechanics and Continuum Models
Peter A. Kollman,Irina Massova,Carolina M. Reyes,Bernd Kuhn,Shuanghong Huo,Lillian T. Chong,Matthew Lee,Tai-Sung Lee,Yong Duan,Wei Wang,Oreola Donini,Piotr Cieplak,Jaysharee Srinivasan,David A. Case,Thomas E. Cheatham +14 more
TL;DR: A historical perspective on the application of molecular dynamics to biological macromolecules is presented and recent developments combining state-of-the-art force fields with continuum solvation calculations have allowed for the fourth era of MD applications in which one can often derive both accurate structure and accurate relative free energies from molecular dynamics trajectories.
Journal ArticleDOI
g_mmpbsa--a GROMACS tool for high-throughput MM-PBSA calculations.
TL;DR: A new tool, g_mmpbsa, which implements the MM-PBSA approach using subroutines written in-house or sourced from the GROMACS and APBS packages is described, and the calculated interaction energy of 37 structurally diverse HIV-1 protease inhibitor complexes is compared.
Journal ArticleDOI
MMPBSA.py: An Efficient Program for End-State Free Energy Calculations.
Bill R. Miller,T. Dwight McGee,Jason M. Swails,Nadine Homeyer,Holger Gohlke,Adrian E. Roitberg +5 more
TL;DR: MMPBSA.py is a program written in Python for streamlining end-state free energy calculations using ensembles derived from molecular dynamics or Monte Carlo simulations, including the Poisson-Boltzmann Model and several implicit solvation models.
Journal ArticleDOI
Assessing the performance of the MM/PBSA and MM/GBSA methods. 1. The accuracy of binding free energy calculations based on molecular dynamics simulations.
TL;DR: An extensive study of 59 ligands interacting with six different proteins finds that MM/PBSA can serve as a powerful tool in drug design, where correct ranking of inhibitors is often emphasized, and the accuracy of the binding free energies calculated by three Generalized Born (GB) models is evaluated.
Journal ArticleDOI
Continuum Solvent Studies of the Stability of DNA, RNA, and Phosphoramidate−DNA Helices
TL;DR: This paper applied continuum solvent models to investigate the relative stability of A-and B-form helices for three DNA sequences, d(CCAACGTTGG), d(ACCCGCGGGT), and d(CGCGAATTCGCG)2, a phosphoramidate-mod...