QuantumBio’s Lance Westerhoff will give a scientific presentation, “Fast, Routine, Absolute Binding Free Energy Calculations Using MovableType in MOE” at the Chemical Computing Group (CCG) 2023 North American Users Group Meeting (UGM) and Conference in Montreal, Canada, on Thursday, June 22, 2023.
QuantumBio is honored to be part of this collaborative scientific event. Our team looks forward to seeing you at the CCG UGM and Conference July 20 – 23, 2023.
Abstract: Fast, Routine, Absolute Binding Free Energy Calculations Using MoveableType in MOE
Energy sampling against biomolecular ensembles has been a significant interest for decades, and with recent advances in the field, interest in these methods has only grown. The multi-dimensional integral of the partition function is analytically inaccessible which has led to the development and application of numerical approximations for molecular ensemble sampling and partition function calculation. Unfortunately, these often-complicated conventional methods are generally CPU-intensive due to their reliance on molecular dynamics for sampling.
With our MovableType (MT), sampling has been divided into two regimes – local and global – which allows one to obtain results which are comparable to conventional free energy methods but at much less computational cost. Local sampling works by separating the inter/intra-molecular energy into pair potentials and simulating molecular energies through pair potential sampling and (re)combination. Meanwhile, global sampling can include output generated from a continuum of methods ranging from docking, cross-docking, rotamer enumeration, approximate and enhanced molecular dynamics (MD), and full MD/MC. This absolute free energy method has already proven itself to be highly predictive in over 60 target:ligand benchmark sets as discussed in the literature below, and additional sets are being added all the time.
In the last year, MT has been fully integrated with MOE and it can be executed locally, through a web service, or even on-demand via a cloud-based backend. With this integration, MOE users can utilize standard MDB files generated through MOE’s simulation and docking infrastructure to make MT available within routine drug discovery campaigns.
- Zheng, Z., M.N. Ucisik, and K.M. Merz, Jr., The Movable Type Method Applied to Protein–Ligand Binding. Journal of Chemical Theory and Computation, 2013. 9(12): p. 5526–5538. https://doi.org/10.1021/ct4005992
- Zheng, Z., O.Y. Borbulevych, H. Liu, J. Deng, R.I. Martin, and L.M. Westerhoff, MovableType Software for Fast Free Energy-Based Virtual Screening: Protocol Development, Deployment, Validation, and Assessment. J Chem Inf Model, 2020. 60(11): p. 5437-5456. https://doi.org/10.1021/acs.jcim.0c00618
- Westerhoff, L.M. and Z. Zheng, Fast, Routine Free Energy of Binding Estimation Using MovableType, in Free Energy Methods in Drug Discovery: Current State and Future Directions, K.A. Armacost and D.C. Thompson, Editors. 2021, American Chemical Society. p. 247-265. https://pubs.acs.org/doi/book/10.1021/bk-2021-1397
- Liu, W., Z. Liu, H. Liu, L.M. Westerhoff, and Z. Zheng, Free Energy Calculations Using the Movable Type Method with Molecular Dynamics Driven Protein-Ligand Sampling. J Chem Inf Model, 2022. 62(22): p. 5645-5665. https://doi.org/10.1021/acs.jcim.2c00278
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