Related papers: Implicit Ligand Theory: Rigorous Binding Free Ener…
We present a differentiable formalism for learning free energies that is capable of capturing arbitrarily complex model dependencies on coarse-grained coordinates and finite-temperature response to variation of general system parameters.…
We present receptor hopping and receptor swapping free energy estimation protocols based on the Alchemical Transfer Method (ATM) to model the binding selectivity of a set of ligands to two arbitrary receptors. The receptor hopping protocol,…
The molecular distributions obtained from canonical Monte Carlo simulations can be used to find an approximate interaction energy. This serves as the basis of a method for estimating the binding free energy for a ligand to a protein which…
Most widely used ligand docking methods assume a rigid protein structure. This leads to problems when the structure of the target protein deforms upon ligand binding. In particular, the ligand's true binding pose is often scored very…
The theory of receptor-ligand binding equilibria has long been well-established in biochemistry, and was primarily constructed to describe dilute aqueous solutions. Accordingly, few computational approaches have been developed for making…
Absolute Binding Free Energy (ABFE) methods are among the most accurate computational techniques for predicting protein-ligand binding affinities, but their utility is limited by the need for many simulations of alchemically modified…
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…
We utilize a multiscale modeling framework to study the effect of shape, size and ligand composition on the efficacy of binding of a ligand-coated-particle to a substrate functionalized with the target receptors. First, we show how…
Prediction of protein-ligand binding affinity is a major goal in drug discovery. Generally, free energy gap is calculated between two states (e.g., ligand binding and unbinding). The energy gap implicitly includes the effects of changes in…
We propose and justify a new approach for fast calculation of the electrostatic interaction energy of clusters of charged particles in constrained energy minimization in the framework of rigid protein-ligand docking. Our ``blind search''…
Recently \1, we presented a general theory for calculat- ing the strength and properties of colloidal interactions mediated by ligand-receptor bonds (such as those that bind DNA-coated colloids). In this communication, we derive a…
Cells measure concentrations of external ligands by capturing ligand molecules with cell surface receptors. The numbers of molecules captured by different receptors co-vary because they depend on the same extrinsic ligand fluctuations.…
We consider membranes adhered through specific receptor-ligand bonds. Thermal undulations of the membrane induce effective interactions between adhesion sites. We derive an upper bound to the free energy that is independent of interaction…
In this contribution I critically revise the alchemical reversible approach in the context of the statistical mechanics theory of non covalent bonding in drug receptor systems. I show that most of the pitfalls and entanglements for the…
We present a simple yet accurate numerical approach to compute the free energy of binding of multivalent objects on a receptor-coated surface. The method correctly accounts for the fact that one ligand can bind to at most one receptor. The…
The calculation of thermodynamic properties of biochemical systems typically requires the use of resource-intensive molecular simulation methods. One example thereof is the thermodynamic profiling of hydration sites, i.e. high-probability…
We develop inductive biases for the machine learning of complex physical systems based on the port-Hamiltonian formalism. To satisfy by construction the principles of thermodynamics in the learned physics (conservation of energy,…
Quantum--Mechanical methods that are both computationally fast and accurate are not yet available for electronic excitations having charge transfer character. In this work, we present a significant step forward towards this goal for those…
Alchemical Grid Dock (AlGDock) is open-source software designed to compute the binding potential of mean force (BPMF) - the binding free energy between a flexible ligand and a rigid receptor - for a small organic ligand and a biological…
Intracellular signaling often arises from ligand-induced oligomerization of cell surface receptors. This oligomerization or clustering process is fundamentally a cooperative behavior between near-neighbor receptor molecules; the properties…