COMPUTATIONAL BIOPHYSICS • MOLECULAR MECHANICS / POISSON-BOLTZMANN (MM-PBSA)

Protein-Ligand Affinity & Binding Thermodynamics

Simulate receptor-ligand complex energetics and non-covalent interaction networks. Quantify Gibbs free energy of binding (ΔG), dissociation constant (Kd), buried accessible surface area (ΔSASA), and enthalpy-entropy compensation.

Drug-Target Complex:

PDB: 7VH8 Open Sidecar 3D

3D Binding Pocket & Contact Surface

Streaming Atomic Coordinates...

Receptor (Cartoon) Inhibitor (Sticks) Key Contact Residues

Temperature (T): 298.15 K (25°C)

Ionic Strength (I): 150 mM

Dielectric Constant (ε): 4.0 (Pocket)

Free Energy of Binding (ΔG) SARS-CoV-2 Mpro

-11.40 kcal/mol

Dissociation Constant (Kd): 3.10 nM Picomolar / High Nanomolar

van der Waals (ΔH_vdW): -16.5 kcal/mol

Electrostatic (ΔH_elec): -8.2 kcal/mol

Conformational Entropy (-TΔS): +9.8 kcal/mol

Desolvation Penalty (ΔG_solv): +3.5 kcal/mol

Biophysical Pocket & Efficiency Metrics

Buried SASA (ΔSASA) 840 Å²

H-Bond Network 5 Contacts

Ligand Efficiency (LE) 0.34 kcal/mol/HA

Lipophilic Efficiency (LipE) 5.82

Catalytic / Key Pocket Residues:

MM-PBSA Thermodynamic Theory

Combines molecular mechanics gas-phase interaction energies with continuum solvent Poisson-Boltzmann electrostatics and SASA-dependent non-polar cavity formation energies.

Ligand Efficiency (LE) Standard

Normalized binding energy per non-hydrogen heavy atom: \(LE = -\Delta G / N_{\text{heavy}}\). Values above 0.30 kcal/mol/HA indicate optimal drug-likeness.

DeepMind Sidecar Direct Link

Fully compatible with the sidecar viewer (sidecar://science/biomolecular-structure-viewer). Inspect hydrogen bond geometry and van der Waals clashes in real time.