Related papers: Precise binding free energy calculations for multi…

Batched synthesis and testing of molecular designs is the key bottleneck of drug development. There has been great interest in leveraging biomolecular foundation models as surrogates to accelerate this process. In this work, we show how to…

The Alchemical Transfer Method (ATM) for the calculation of standard binding free energies of non-covalent molecular complexes is presented. The method is based on a coordinate displacement perturbation of the ligand between the receptor…

Accurate prediction of molecular vibrational frequencies is important to identify spectroscopic signatures and reaction thermodynamics. In this work, we develop a method to quantify uncertainty associated with density functional theory…

Generating ligand molecules for specific protein targets, known as structure-based drug design, is a fundamental problem in therapeutics development and biological discovery. Recently, target-aware generative models, especially diffusion…

In the present work, we present a hybrid quantum-classical workflow aimed at improving the accuracy of alchemical free energy (AFE) predictions by incorporating configuration interaction (CI) simulations using the book-ending correction…

From the onset of fundamental statistical mechanical constructs formulated in the late 19th century, alchemical free-energy methods slowly emerged and transitioned to become operational tools of biomolecular simulation applicable to a wide…

Accurate prediction of protein active-site structures remains a central challenge in structural biology, particularly for short and flexible peptide fragments where conventional and simulation-based methods often fail. Here, we present a…

Calculating free energy differences is a topic of substantial interest and has many applications including molecular docking and hydration, solvation, and binding free energies which is used in computational drug discovery. However, in…

Despite recent advances in protein-ligand structure prediction, deep learning methods remain limited in their ability to accurately predict binding affinities, particularly for novel protein targets dissimilar from the training set. In…

Predictions of relative stabilities of (competing) molecular crystals are of great technological relevance, most notably for the pharmaceutical industry. However, they present a long-standing challenge for modeling, as often minuscule free…

We describe a two-step approach for combining interactive molecular dynamics in virtual reality (iMD-VR) with free energy (FE) calculation to explore the dynamics of biological processes at the molecular level. We refer to this combined…

We present a novel inference algorithm for arbitrary, binary, undirected graphs. Unlike loopy belief propagation, which iterates fixed point equations, we directly descend on the Bethe free energy. The algorithm consists of two phases,…

The ability to predict accurate thermodynamic and kinetic properties in biomolecular systems is of both scientific and practical utility. While both remain very difficult, predictions of kinetics are particularly difficult because rates, in…

Multi fidelity Bayesian optimization (MFBO) leverages experimental and or computational data of varying quality and resource cost to optimize towards desired maxima cost effectively. This approach is particularly attractive for chemical…

Accurate prediction of protein-ligand binding affinity is crucial for rapid and efficient drug development. Recently, the importance of predicting binding affinity has led to increased attention on research that models the three-dimensional…

We present an Adaptively Biased Molecular Dynamics (ABMD) method for the computation of the free energy surface of a reaction coordinate using non-equilibrium dynamics. The ABMD method belongs to the general category of umbrella sampling…

Motivation: Modeling biological signaling networks using ordinary differential equations (ODEs) has proven to be a powerful technique for generating insight into cellular dynamics, but it typically requires estimating rate parameters based…

Exact exchange contributions are known to crucially affect electronic states, which in turn govern covalent bond formation and breaking in chemical species. Empirically averaging the exact exchange admixture over compositional degrees of…

The Targeted Free Energy Perturbation (TFEP) method aims to overcome the time-consuming and computer-intensive stratification process of standard methods for estimating the free energy difference between two states. To achieve this, TFEP…

One reason that free energy difference calculations are notoriously difficult in molecular systems is due to insufficient conformational overlap, or similarity, between the two states or systems of interest. The degree of overlap is…