相关论文: A streamlined, general approach for computing liga…
A molecular model is proposed of a bilayer consisting of fully saturated DPPC and mono unsaturated DOPC. The model not only encompasses the constant density within the hydrophobic core of the bilayer, but also the tendency of chain segments…
Host-guest binding plays a crucial role in the functionality of various systems, and its efficiency is often quantified using the binding free energy, which represents the free-energy difference between the bound and dissociated states.…
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…
We develop a simple but rigorous model of protein-protein association kinetics based on diffusional association on free energy landscapes obtained by sampling configurations within and surrounding the native complex binding funnels. Guided…
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…
Free energy perturbation (FEP) is considered the gold-standard simulation method for estimating small molecule binding affinity, a quantity of vital importance to drug discovery. The accuracy of FEP critically depends on an accurate model…
Specific binding of proteins to DNA is one of the most common ways in which gene expression is controlled. Although general rules for the DNA-protein recognition can be derived, the ambiguous and complex nature of this mechanism precludes a…
Random lateral translocation of lipids and proteins is a universal process on membrane surfaces. Local aggregation or organization of lipids and proteins can be induced when this lateral random diffusion is mediated by the electrostatic…
Molecular docking is a key task in computational biology that has attracted increasing interest from the machine learning community. While existing methods have achieved success, they generally treat each protein-ligand pair in isolation.…
Membrane proteins typically deform the surrounding lipid bilayer membrane, which can play an important role in the function, regulation, and organization of membrane proteins. Membrane elasticity theory provides a beautiful description of…
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,…
A cell membrane can be simply regarded as composite material consisting of lipid bilayer, membrane cytoskeleton beneath lipid bilayer, and proteins embedded in lipid bilayer and linked with membrane cytoskeleton if one only concerns its…
Predicting accurate protein-ligand binding affinity is important in drug discovery but remains a challenge even with computationally expensive biophysics-based energy scoring methods and state-of-the-art deep learning approaches. Despite…
The study of a receptor-ligand system generally relies on the analysis of its dose-response (or concentration-effect) curve, which quantifies the relation between ligand concentration and the biological effect (or cellular response) induced…
We compute absolute binding affinities for two ligands bound to the FKBP protein using non-equilibrium unbinding simulations. The methodology is straight-forward, requiring little or no modification to many modern molecular simulation…
The cell membrane is inherently asymmetric and heterogeneous in its composition, a feature that is crucial for its function. Using atomistic molecular dynamics simulations, the physical properties of a 3-component asymmetric mixed lipid…
The theory behind computation of absolute binding free energies using explicit-solvent molecular simulations is well-established, yet somewhat complex, with counter-intuitive aspects. This leads to frequent frustration, common…
G-protein-coupled receptors (GPCRs), primary targets for over one-third of approved therapeutics, rely on intricate conformational transitions to transduce signals. While Molecular Dynamics (MD) is essential for elucidating this…
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…
The spatial organization of complex biochemical reactions is essential for the regulation of cellular processes. Membrane-less structures called foci containing high concentrations of specific proteins have been reported in a variety of…