相关论文: A streamlined, general approach for computing liga…
Confined hydration and conformational flexibility are some of the challenges encountered for the rational design of selective antagonists of G-protein coupled receptors. We present a set of C3-substituted (-)-stepholidine derivatives as…
Computing equilibrium concentrations of molecular complexes is generally analytically intractable and requires numerical approaches. In this work we focus on the polymer-monomer level, where indivisible molecules (monomers) combine to form…
Understanding how different classes of molecules move across biological membranes is a prerequisite to predicting a solute's permeation rate, which is a critical factor in the fields of drug design and pharmacology. We use biased Molecular…
The adhesion of cells is mediated by receptors and ligands anchored in apposing membranes. A central question is how to characterize the binding affinity of these membrane-anchored molecules. For soluble molecules, the binding affinity is…
We introduce a derangement model of ligand-receptor binding that allows us to quantitatively frame the question "How can ligands seek out and bind to their optimal receptor sites in a sea of other competing ligands and suboptimal receptor…
Understanding design principles of biomolecular recognition is a key question of molecular biology. Yet the enormous complexity and diversity of biological molecules hamper the efforts to gain a predictive ability for the free energy of…
In multi-resolution simulations, different system components are simultaneously modelled at different levels of resolution, these being smoothly coupled together. In the case of enzyme systems, computationally expensive atomistic detail is…
The phase separation in lipid bilayers that include negatively charged lipids is examined experimentally. We observed phase-separated structures and determined the membrane miscibility temperatures in several binary and ternary lipid…
Free energy calculations are rapidly becoming indispensable in structure-enabled drug discovery programs. As new methods, force fields, and implementations are developed, assessing their expected accuracy on real-world systems…
The concept of a protein diffusing in its free energy folding landscape has been fruitful for both theory and experiment. Yet the choice of the reaction coordinate (RC) introduces an undesirable degree of arbitrariness into the problem. We…
Although the importance of protein dynamics in protein function is generally recognized, the role of protein fluctuations in allosteric effects scarcely has been considered. To address this gap, the Kullback-Leibler divergence (Dx) between…
We present the multicomponent functionalized free energies that characterize the low-energy packings of amphiphilic molecules within a membrane through a correspondence to connecting orbits within a reduced dynamical system. To each…
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…
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…
The massively parallel computation of absolute binding free energy with a well-equilibrated system (MP-CAFEE) has been developed [H. Fujitani, Y. Tanida, M. Ito, G. Jayachandran, C. D. Snow, M. R. Shirts, E. J. Sorin, and V. S. Pande, J.…
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…
We present a dynamical model of lipoprotein metabolism derived by combining a cascading process in the blood stream and cellular level regulatory dynamics. We analyse the existence and stability of equilibria and show that this…
The efficacy of drug treatments depends on how tightly small molecules bind to their target proteins. The rapid and accurate quantification of the strength of these interactions (as measured by binding affinity) is a grand challenge of…
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…
The prediction of protein-ligand binding affinity is of great significance for discovering lead compounds in drug research. Facing this challenging task, most existing prediction methods rely on the topological and/or spatial structure of…