Author(s)
Yinglong Miao
Published 4 Projects
Biochemistry Biophysics Accelerated Molecular Dynamics Gamd Mass Spectrometry Ms Western Blotting
Apurba Bhattarai
Graduate Research Assistant and Ph.D. Candidate, University of Kansas
Field of Study: Biology , Published 5 Projects
Content
Video Abstract (AI generated) (01:50) Paper Preprint Supporting Information Movie S1 Movie S2 Movie S3 Movie S4 Movie S5 Journal of Chemical Theory and ComputationCalculations of ligand binding free energies and kinetic rates are important for drug design. However, such tasks have proven challenging in computational chemistry and biophysics. To address this challenge, we have developed a new computational method "LiGaMD", which selectively boosts the ligand non-bonded interaction potential energy based on the Gaussian accelerated molecular dynamics (GaMD) enhanced sampling technique. Another boost potential could be applied to the remaining potential energy of the entire system in a dual-boost algorithm (LiGaMD_Dual) to facilitate ligand binding. LiGaMD has been demonstrated on host-guest and protein-ligand binding model systems. Repetitive guest binding and unbinding in the β-cyclodextrin host were observed in hundreds-of-nanosecond LiGaMD simulations. The calculated binding free energies of guest molecules with sufficient sampling agreed excellently with experimental data (< 1.0 kcal/mol error). In comparison with previous microsecond-timescale conventional molecular dynamics simulations, accelerations of ligand kinetic rate constants in LiGaMD simulations were properly estimated using Kramers' rate theory. Furthermore, LiGaMD allowed us to capture repetitive dissociation and binding of the benzamidine inhibitor in trypsin within 1 μs simulations. The calculated ligand binding free energy and kinetic rate constants compared well with the experimental data. In summary, LiGaMD provides a promising approach for characterizing ligand binding thermodynamics and kinetics simultaneously, which is expected to facilitate computer-aided drug design. ### Competing Interest Statement The authors have declared no competing interest.
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Apurba Bhattarai. (2021, Nov 5).Ligand Gaussian accelerated molecular dynamics (LiGaMD): Characterization of ligand binding thermodynamics and kinetics[Video]. Scitok. https://scitok.com/project/p/59691d33
Miao Yinglong. "Ligand Gaussian accelerated molecular dynamics (LiGaMD): Characterization of ligand binding thermodynamics and kinetics" Scitok, uploaded by Bhattarai Apurba, 5 Nov, 2021, https://scitok.com/project/p59691d33
Apurba Bhattarai. "Ligand Gaussian accelerated molecular dynamics (LiGaMD): Characterization of ligand binding thermodynamics and kinetics" Scitok. (Nov 5, 2021). https://scitok.com/project/p/59691d33
Apurba Bhattarai (Nov 5, 2021). Ligand Gaussian accelerated molecular dynamics (LiGaMD): Characterization of ligand binding thermodynamics and kinetics Scitok. https://scitok.com/project/p/59691d33
Apurba Bhattarai. Ligand Gaussian accelerated molecular dynamics (LiGaMD): Characterization of ligand binding thermodynamics and kinetics[video]. 2021 Nov 5. https://scitok.com/project/p/59691d33
@online{al2006link, title={ Ligand Gaussian accelerated molecular dynamics (LiGaMD): Characterization of ligand binding thermodynamics and kinetics }, author={ Bhattarai, Apurba }, organization={Scitok}, month={ Nov }, day={ 5 }, year={ 2021 }, url = {https://scitok.com/project/p/59691d33}, }