Related papers: A streamlined, general approach for computing liga…
Area per molecule in a DPPC-Cholesterol bilayers depends non-linearly on the cholesterol concentration. Using flexible strings model of lipid membranes we calculate area per molecule in DPPC-Cholesterol mixtures in the biologically relevant…
The adhesion of biological membranes is mediated by the binding of membrane-anchored receptor and ligand proteins. Central questions are how the binding kinetics of these proteins is affected by the membranes and by the membrane anchoring…
A rigorous formalism for estimating noncovalent binding free energies and thermodynamic expectations from calculations in which receptor configurations are sampled independently from the ligand is derived. Due to this separation, receptor…
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 new method that combines alchemical transformation with physical pathway to accurately and efficiently compute the absolute binding free energy of receptor-ligand complex. Currently, the double decoupling method (DDM) and the…
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…
Alchemical binding free energy (BFE) calculations offer an efficient and thermodynamically rigorous approach to in silico binding affinity predictions. As a result of decades of methodological improvements and recent advances in computer…
Hydrophobic thickness mismatch between integral membrane proteins and the surrounding lipid bilayer can produce lipid bilayer thickness deformations. Experiment and theory have shown that protein-induced lipid bilayer thickness deformations…
We present a parameterized analytical model of alchemical molecular binding. The model describes accurately the free energy profiles of linear single-decoupling alchemical binding free energy calculations. The parameters of the model, which…
The assembly of proteins in membranes plays a key role in many crucial cellular pathways. Despite their importance, characterizing transmembrane assembly remains challenging for experiments and simulations. Equilibrium molecular dynamics…
Accurate prediction of binding free energies is critical to streamlining the drug development and protein design process. With the advent of GPU acceleration, absolute alchemical methods, which simulate the removal of ligand electrostatics…
Background. The calculation of diffusion-controlled ligand binding rates is important for understanding enzyme mechanisms as well as designing enzyme inhibitors. We demonstrate the accuracy and effectiveness of a Lagrangian particle-based…
Equilibrating proteins and other biomacromolecules is cardinal for molecular dynamics simulation of such biological systems in which they perform free dynamics without any externally-applied mechanical constraint, until thermodynamic…
The adhesion of cell membranes is mediated by the binding of membrane-anchored receptor and ligand proteins. In this article, we review recent results from simulations and theory that lead to novel insights on how the binding equilibrium…
Many biologically important ligands of proteins are large, flexible, and often charged molecules that bind to extended regions on the protein surface. It is infeasible or expensive to locate such ligands on proteins with standard methods…
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…
The phenomenon of molecular binding, where two molecules, referred to as a receptor and a ligand, bind together to form a ligand-receptor complex, is ubiquitous in biology and essential for the accurate functioning of all life-sustaining…
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…
Lipid membranes have complex compositions and modeling the thermodynamic properties of multi-component lipid systems remains a remote goal. In this work we attempt to describe the thermodynamics of binary lipid mixtures by mapping…
Resistance to chemotherapy and molecularly targeted therapies is a major factor in limiting the effectiveness of cancer treatment. In many cases, resistance can be linked to genetic changes in target proteins, either pre-existing or…