[HTML][HTML] A guide to in silico drug design

Y Chang, BA Hawkins, JJ Du, PW Groundwater… - Pharmaceutics, 2023 - mdpi.com
The drug discovery process is a rocky path that is full of challenges, with the result that very
few candidates progress from hit compound to a commercially available product, often due …

Alchemical transformations and beyond: Recent advances and real-world applications of free energy calculations in drug discovery

R Qian, J Xue, Y Xu, J Huang - Journal of Chemical Information …, 2024 - ACS Publications
Computational methods constitute efficient strategies for screening and optimizing potential
drug molecules. A critical factor in this process is the binding affinity between candidate …

Accurate prediction of GPCR ligand binding affinity with free energy perturbation

F Deflorian, L Perez-Benito, EB Lenselink… - Journal of Chemical …, 2020 - ACS Publications
The computational prediction of relative binding free energies is a crucial goal for drug
discovery, and G protein-coupled receptors (GPCRs) are arguably the most important drug …

Predicting the mutation effects of protein–ligand interactions via end-point binding free energy calculations: strategies and analyses

Y Yu, Z Wang, L Wang, S Tian, T Hou, H Sun - Journal of Cheminformatics, 2022 - Springer
Protein mutations occur frequently in biological systems, which may impact, for example, the
binding of drugs to their targets through impairing the critical H-bonds, changing the …

Computational studies of protein–drug binding affinity changes upon mutations in the drug target

R Friedman - Wiley Interdisciplinary Reviews: Computational …, 2022 - Wiley Online Library
Mutations that lead to drug resistance limit the efficacy of antibiotics, antiviral drugs, targeted
cancer therapies, and other treatments. Accurately calculating protein–drug binding affinity …

Improving the accuracy of protein thermostability predictions for single point mutations

J Duan, D Lupyan, L Wang - Biophysical Journal, 2020 - cell.com
Accurately predicting the protein thermostability changes upon single point mutations in
silico is a challenge that has implications for understanding diseases as well as industrial …

Large-scale application of free energy perturbation calculations for antibody design

F Zhu, FA Bourguet, WFD Bennett, EY Lau, KT Arrildt… - Scientific Reports, 2022 - nature.com
Alchemical free energy perturbation (FEP) is a rigorous and powerful technique to calculate
the free energy difference between distinct chemical systems. Here we report our …

Selection pressures on evolution of ribonuclease H explored with rigorous free–energy–based design

RL Hayes, CF Nixon, S Marqusee… - Proceedings of the …, 2024 - pnas.org
Understanding natural protein evolution and designing novel proteins are motivating interest
in development of high-throughput methods to explore large sequence spaces. In this work …

[PDF][PDF] Principles of cold adaptation of fish lactate dehydrogenases revealed by computer simulations of the catalytic reaction

L Koenekoop, J Åqvist - Molecular biology and evolution, 2023 - academic.oup.com
Cold-adapted enzymes from psychrophilic and psychrotolerant species are characterized by
a higher catalytic activity at low temperature than their mesophilic orthologs and are also …

Characterizing and explaining the impact of disease-associated mutations in proteins without known structures or structural homologs

N Sen, I Anishchenko, N Bordin, I Sillitoe… - Briefings in …, 2022 - academic.oup.com
Mutations in human proteins lead to diseases. The structure of these proteins can help
understand the mechanism of such diseases and develop therapeutics against them. With …