AIMC Topic: Molecular Dynamics Simulation

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Classical and Machine Learning Methods for Protein - Ligand Binding Free Energy Estimation.

Current drug metabolism
Binding free energy estimation of drug candidates to their biomolecular target is one of the best quantitative estimators in computer-aided drug discovery. Accurate binding free energy estimation is still a challengeable task even after decades of re...

Machine learning prediction of antibody aggregation and viscosity for high concentration formulation development of protein therapeutics.

mAbs
Machine learning has been recently used to predict therapeutic antibody aggregation rates and viscosity at high concentrations (150 mg/ml). These works focused on commercially available antibodies, which may have been optimized for stability. In this...

Progress in deep Markov state modeling: Coarse graining and experimental data restraints.

The Journal of chemical physics
Recent advances in deep learning frameworks have established valuable tools for analyzing the long-timescale behavior of complex systems, such as proteins. In particular, the inclusion of physical constraints, e.g., time-reversibility, was a crucial ...

Machine learning builds full-QM precision protein force fields in seconds.

Briefings in bioinformatics
Full-quantum mechanics (QM) calculations are extraordinarily precise but difficult to apply to large systems, such as biomolecules. Motivated by the massive demand for efficient calculations for large systems at the full-QM level and by the significa...

Computational prediction of the effect of amino acid changes on the binding affinity between SARS-CoV-2 spike RBD and human ACE2.

Proceedings of the National Academy of Sciences of the United States of America
The association of the receptor binding domain (RBD) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein with human angiotensin-converting enzyme 2 (hACE2) represents the first required step for cellular entry. SARS-CoV-2 ha...

A deep autoencoder framework for discovery of metastable ensembles in biomacromolecules.

The Journal of chemical physics
Biomacromolecules manifest dynamic conformational fluctuation and involve mutual interconversion among metastable states. A robust mapping of their conformational landscape often requires the low-dimensional projection of the conformational ensemble ...

Improving the accuracy and convergence of drug permeation simulations via machine-learned collective variables.

The Journal of chemical physics
Understanding the permeation of biomolecules through cellular membranes is critical for many biotechnological applications, including targeted drug delivery, pathogen detection, and the development of new antibiotics. To this end, computer simulation...

Computational studies of anaplastic lymphoma kinase mutations reveal common mechanisms of oncogenic activation.

Proceedings of the National Academy of Sciences of the United States of America
Kinases play important roles in diverse cellular processes, including signaling, differentiation, proliferation, and metabolism. They are frequently mutated in cancer and are the targets of a large number of specific inhibitors. Surveys of cancer gen...

Computational Ion Channel Research: from the Application of Artificial Intelligence to Molecular Dynamics Simulations.

Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
Although ion channels are crucial in many physiological processes and constitute an important class of drug targets, much is still unclear about their function and possible malfunctions that lead to diseases. In recent years, computational methods ha...

Calculation of therapeutic antibody viscosity with coarse-grained models, hydrodynamic calculations and machine learning-based parameters.

mAbs
High viscosity presents a challenge for manufacturing and drug delivery of therapeutic antibodies. The viscosity is determined by protein-protein interactions among many antibodies. Molecular simulation is a promising method to study protein-protein ...