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Abstract Gaussian accelerated molecular dynamics (GaMD) is a robust computational method for simultaneous unconstrained enhanced sampling and free energy calculations of biomolecules. It works by adding a harmonic boost potential to smooth biomolecular potential energy surface and reduce energy barriers. GaMD greatly accelerates biomolecular simulations by orders of magnitude. Without the need to set predefined reaction coordinates or collective variables, GaMD provides unconstrained enhanced sampling and is advantageous for simulating complex biological processes. The GaMD boost potential exhibits a Gaussian distribution, thereby allowing for energetic reweighting via cumulant expansion to the second order (i.e., “Gaussian approximation”). This leads to accurate reconstruction of free energy landscapes of biomolecules. Hybrid schemes with other enhanced sampling methods, such as the replica‐exchange GaMD (rex‐GaMD) and replica‐exchange umbrella sampling GaMD (GaREUS), have also been introduced, further improving sampling and free energy calculations. Recently, new “selective GaMD” algorithms including the Ligand GaMD (LiGaMD) and Peptide GaMD (Pep‐GaMD) enabled microsecond simulations to capture repetitive dissociation and binding of small‐molecule ligands and highly flexible peptides. The simulations then allowed highly efficient quantitative characterization of the ligand/peptide binding thermodynamics and kinetics. Taken together, GaMD and its innovative variants are applicable to simulate a wide variety of biomolecular dynamics, including protein folding, conformational changes and allostery, ligand binding, peptide binding, protein–protein/nucleic acid/carbohydrate interactions, and carbohydrate/nucleic acid interactions. In this review, we present principles of the GaMD algorithms and recent applications in biomolecular simulations and drug design. This article is categorized under:Structure and Mechanism > Computational Biochemistry and BiophysicsMolecular and Statistical Mechanics > Molecular Dynamics and Monte‐Carlo MethodsMolecular and Statistical Mechanics > Free Energy Methods
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Nearest‐neighbor sparse Cholesky matrices in spatial statistics
Abstract Gaussian process (GP) is a staple in the toolkit of a spatial statistician. Well‐documented computing roadblocks in the analysis of large geospatial datasets using GPs have now largely been mitigated via several recent statistical innovations. Nearest neighbor Gaussian process (NNGP) has emerged as one of the leading candidates for such massive‐scale geospatial analysis owing to their empirical success. This article reviews the connection of NNGP to sparse Cholesky factors of the spatial precision (inverse‐covariance) matrix. Focus of the review is on these sparse Cholesky matrices which are versatile and have recently found many diverse applications beyond the primary usage of NNGP for fast parameter estimation and prediction in the spatial (generalized) linear models. In particular, we discuss applications of sparse NNGP Cholesky matrices to address multifaceted computational issues in spatial bootstrapping, simulation of large‐scale realizations of Gaussian random fields, and extensions to nonparametric mean function estimation of a GP using random forests. We also review a sparse‐Cholesky‐based model for areal (geographically aggregated) data that addresses long‐established interpretability issues of existing areal models. Finally, we highlight some yet‐to‐be‐addressed issues of such sparse Cholesky approximations that warrant further research. This article is categorized under:Algorithms and Computational Methods > AlgorithmsAlgorithms and Computational Methods > Numerical Methods
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- Award ID(s):
- 1915803
- PAR ID:
- 10370901
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- WIREs Computational Statistics
- Volume:
- 14
- Issue:
- 5
- ISSN:
- 1939-5108
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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