Recent developments in free energy calculations for drug discovery

E King, E Aitchison, H Li, R Luo - Frontiers in Molecular Biosciences, 2021 - frontiersin.org
The grand challenge in structure-based drug design is achieving accurate prediction of
binding free energies. Molecular dynamics (MD) simulations enable modeling of …

[HTML][HTML] Recent developments in multiscale free energy simulations

EP Barros, B Ries, L Böselt, C Champion… - Current Opinion in …, 2022 - Elsevier
Physics-based free energy simulations enable the rigorous calculation of properties, such as
conformational equilibria, solvation or binding free energies. While historically most …

Accurate binding free energy method from end-state MD simulations

E Akkus, O Tayfuroglu, M Yildiz… - Journal of Chemical …, 2022 - ACS Publications
Herein, we introduce a new strategy to estimate binding free energies using end-state
molecular dynamics simulation trajectories. The method is adopted from linear interaction …

Molecular simulations of conformational transitions within the insulin receptor kinase reveal consensus features in a multistep activation pathway

K Nam, Y Tao, V Ovchinnikov - The Journal of Physical Chemistry …, 2023 - ACS Publications
Modulating the transitions between active and inactive conformations of protein kinases is
the primary means of regulating their catalytic activity, achieved by phosphorylation of the …

Atomistic and Thermodynamic Analysis of N6-Methyladenosine (m6A) Recognition by the Reader Domain of YTHDC1

Y Li, RK Bedi, L Wiedmer, X Sun… - Journal of Chemical …, 2021 - ACS Publications
N6-Methyladenosine (m6A) is the most frequent modification in eukaryotic messenger RNA
(mRNA) and its cellular processing and functions are regulated by the reader proteins …

Efficient alchemical intermediate states in free energy calculations using λ-enveloping distribution sampling

G König, B Ries, PH Hünenberger… - Journal of Chemical …, 2021 - ACS Publications
Alchemical free energy calculations generally require intermediate states along a coupling
parameter λ to establish sufficient phase space overlap for obtaining converged results …

Deciphering nucleotide modification-induced structure and stability changes

T Hurst, SJ Chen - RNA biology, 2021 - Taylor & Francis
Nucleotide modification in RNA controls a bevy of biological processes, including RNA
degradation, gene expression, and gene editing. In turn, misregulation of modified …

Variational method for networkwide analysis of relative ligand binding free energies with loop closure and experimental constraints

TJ Giese, DM York - Journal of chemical theory and computation, 2021 - ACS Publications
We describe an efficient method for the simultaneous solution of all free energies within a
relative binding free-energy (RBFE) network with cycle closure and experimental/reference …

Development of Multiscale Force Field for Actinide (An3+) Solutions

J Song, X Li, X Xu, J Lu, H Hu, J Li - Journal of Chemical Theory …, 2024 - ACS Publications
A multiscale force field (FF) is developed for an aqueous solution of trivalent actinide cations
An3+ (An= U, Np, Pu, Am, Cm, Bk, and Cf) by using a 12-6-4 Lennard-Jones type potential …

Robust, efficient and automated methods for accurate prediction of protein-ligand binding affinities in AMBER Drug Discovery Boost

TS Lee, HC Tsai, A Ganguly, TJ Giese… - Free Energy Methods in …, 2021 - ACS Publications
Recent concurrent advances in methodology development, computer hardware and
simulation software has transformed our ability to make practical, quantitative predictions of …