Related papers: Boltz-ABFE: Free Energy Perturbation without Cryst…

We present TerraBind, a foundation model for protein-ligand structure and binding affinity prediction that achieves 26-fold faster inference than state-of-the-art methods while improving affinity prediction accuracy by $\sim$20\%. Current…

The Free-Energy-Principle (FEP) is an influential and controversial theory which postulates a deep and powerful connection between the stochastic thermodynamics of self-organization and learning through variational inference. Specifically,…

We present a feature functional theory - binding predictor (FFT-BP) for the protein-ligand binding affinity prediction. The underpinning assumptions of FFT-BP are as follows: i) representability: there exists a microscopic feature vector…

Cryo-electron microscopy (cryo-EM) is a technique for reconstructing the 3-dimensional (3D) structure of biomolecules (especially large protein complexes and molecular assemblies). As the resolution increases to the near-atomic scale,…

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…

The accurate prediction of protein-ligand binding affinities is crucial for drug discovery. Alchemical free energy calculations have become a popular tool for this purpose. However, the accuracy and reliability of these methods can vary…

The minimum free-energy path (MFEP) is the most probable route of the nucleation process on the multidimensional free-energy surface. In this study, the phase-field equation is used as a mathematical tool to deduce the minimum free-energy…

We use a free energy functional theory to elucidate general properties of heterogeneously ordering, fast folding proteins, and we test our conclusions with lattice simulations. We find that both structural and energetic heterogeneity can…

A central problem of materials science is to determine whether a hypothetical material is stable without being synthesized, which is mathematically equivalent to a global optimization problem on a highly non-linear and multi-modal potential…

Based on a generative model (GM) and beliefs over hidden states, the free energy principle (FEP) enables an agent to sense and act by minimizing a free energy bound on Bayesian surprise. Inclusion of prior beliefs in the GM about desired…

Proteins are essential for maintaining life. For example, knowing the structure of a protein, cell regulatory mechanisms of organisms can be modeled, supporting the development of disease treatments or the understanding of relationships…

While all the information required for the folding of a protein is contained in its amino acid sequence, one has not yet learned how to extract this information to predict the three--dimensional, biologically active, native conformation of…

Characterizing conformational transitions in physical systems remains a fundamental challenge, as traditional sampling methods struggle with the high-dimensional nature of molecular systems and high-energy barriers between stable states.…

We have developed a thorough and accurate method of determining anharmonic free energies, the temperature dependent effective potential technique (TDEP). It is based on \emph{ab initio} molecular dynamics followed by a mapping onto a model…

Free energies play a central role in characterising the behaviour of chemical systems and are among the most important quantities that can be calculated by molecular dynamics simulations. Solvation free energies in various organic solvents,…

Based on thermodynamic integration we introduce atoms in molecules (AIM) using the orbital-free framework of alchemical perturbation density functional theory (APDFT). Within APDFT, atomic energies and electron densities in molecules are…

The unique electron deficiency of boron makes it challenging to determine the stable structures, leading to a wide variety of forms. In this work, we introduce a statistical model based on grand canonical ensemble theory that incorporates…

Models that accurately predict properties based on chemical structure are valuable tools in drug discovery. However, for many properties, public and private training sets are typically small, and it is difficult for the models to generalize…

The Free-Energy Principle (FEP) [1-3] has been adopted in a variety of ambitious proposals that aim to characterize all adaptive, sentient, and cognitive systems within a unifying framework. Judging by the amount of attention it has…

The primary objective of most lead optimization campaigns is to enhance the binding affinity of ligands. For large molecules such as antibodies, identifying mutations that enhance antibody affinity is particularly challenging due to the…