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Ligand strain energy, the energy difference between the bound and unbound conformations of a ligand, is an important component of structure-based small molecule drug design. A large majority of observed ligands in protein-small molecule…
Accurately predicting protein-ligand binding free energies (BFEs) remains a central challenge in drug discovery, particularly because the most reliable methods, such as free energy perturbation (FEP), are computationally intensive and…
We report a systematic study of the weak chemical bond between two benzene molecules. We first show that it is possible to obtain a very good description of the C_2 dimer and the benzene molecule, by using pseudopotentials for the…
Designing protein binders targeting specific sites, which requires to generate realistic and functional interaction patterns, is a fundamental challenge in drug discovery. Current structure-based generative models are limited in generating…
Powerful generative AI models of protein-ligand structure have recently been proposed, but few of these methods support both flexible protein-ligand docking and affinity estimation. Of those that do, none can directly model multiple binding…
Computational approaches to drug discovery can reduce the time and cost associated with experimental assays and enable the screening of novel chemotypes. Structure-based drug design methods rely on scoring functions to rank and predict…
Dendritic polyelectrolytes constitute high potential drugs and carrier systems for biomedical purposes, still their biomolecular interaction modes, in particular those determining the binding affinity to proteins, have not been…
We report the results of our participation in the SAMPL8 GDCC Blind Challenge for host-guest binding affinity predictions. Absolute binding affinity prediction is of central importance to the biophysics of molecular association and…
A new kind of Lagrangian diagnostic family is proposed and a specific form of it is suggested for characterizing mixing: the maximal extent of a trajectory (MET). It enables the detection of coherent structures and their dynamics in two-…
The solid-liquid interface free energy \gamma sl is a key parameter controlling nucleation and growth during solidification and other phenomena. There are intrinsic difficulties in obtaining accurate experimental values, and the previous…
We develop a path-based approach to continuous-time random walks on networks with arbitrarily weighted edges. We describe an efficient numerical algorithm for calculating statistical properties of the stochastic path ensemble. After…
Many enhanced sampling techniques rely on the identification of a number of collective variables that describe all the slow modes of the system. By constructing a bias potential in this reduced space one is then able to sample efficiently…
Accurate measurements of kinetic rate constants for interacting biomolecules is crucial for understanding the mechanisms underlying intracellular signalling pathways. The magnitude of binding rates plays a very important molecular…
In epidemiological research, causal models incorporating potential mediators along a pathway are crucial for understanding how exposures influence health outcomes. This work is motivated by integrated epidemiological and blood biomarker…
In many scientific fields, there is an interest in understanding the way in which complex chemical networks evolve. The chemical networks which researchers focus upon, have become increasingly complex and this has motivated the development…
This note considers a system in which three ligands can independently bind to a scaffold. Such systems arise in diverse applications, including immunotherapy and synthetic biology. It is shown that there are unique steady states in each…
The last decade has witnessed a swiftly increasing interest in the design and production of novel multivalent molecules as powerful alternatives for conventional antibodies in the fight against cancer and infectious diseases. However, while…
In this work, we analytically derive the exact closed dynamical equations for a liquid with short-ranged interactions in large spatial dimensions using the same statistical mechanics tools employed to analyze Brownian motion. Our derivation…
Field-theoretical method is proposed, that yields analytical expression for lateral pressure distribution across hydrophobic core of a bilayer lipid membrane. Lipid molecule, repelling entropicaly surrounding neighbors, is modeled as a…
Myoglobin modulates the binding of diatomic molecules to its heme group via hydrogen-bonding and steric interactions with neighboring residues, and is an important benchmark for computational studies of biomolecules. We have performed…