AIMC Topic: Molecular Dynamics Simulation

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An Updated Review of Computer-Aided Drug Design and Its Application to COVID-19.

BioMed research international
The recent outbreak of the deadly coronavirus disease 19 (COVID-19) pandemic poses serious health concerns around the world. The lack of approved drugs or vaccines continues to be a challenge and further necessitates the discovery of new therapeutic ...

A multi-conformational virtual screening approach based on machine learning targeting PI3Kγ.

Molecular diversity
Nowadays, more and more attention has been attracted to develop selective PI3Kγ inhibitors, but the unique structural features of PI3Kγ protein make it a very big challenge. In the present study, a virtual screening strategy based on machine learning...

Discovery of novel DGAT1 inhibitors by combination of machine learning methods, pharmacophore model and 3D-QSAR model.

Molecular diversity
DGAT1 plays a crucial controlling role in triglyceride biosynthetic pathways, which makes it an attractive therapeutic target for obesity. Thus, development of DGAT1 inhibitors with novel chemical scaffolds is desired and important in the drug discov...

CASTELO: clustered atom subtypes aided lead optimization-a combined machine learning and molecular modeling method.

BMC bioinformatics
BACKGROUND: Drug discovery is a multi-stage process that comprises two costly major steps: pre-clinical research and clinical trials. Among its stages, lead optimization easily consumes more than half of the pre-clinical budget. We propose a combined...

Machine learning models to select potential inhibitors of acetylcholinesterase activity from SistematX: a natural products database.

Molecular diversity
Alzheimer's disease is the most common form of dementia, representing 60-70% of dementia cases. The enzyme acetylcholinesterase (AChE) cleaves the ester bonds in acetylcholine and plays an important role in the termination of acetylcholine activity a...

A Deep-Learning Sequence-Based Method to Predict Protein Stability Changes Upon Genetic Variations.

Genes
Several studies have linked disruptions of protein stability and its normal functions to disease. Therefore, during the last few decades, many tools have been developed to predict the free energy changes upon protein residue variations. Most of these...

Machine Learning Reveals the Critical Interactions for SARS-CoV-2 Spike Protein Binding to ACE2.

The journal of physical chemistry letters
SARS-CoV and SARS-CoV-2 bind to the human ACE2 receptor in practically identical conformations, although several residues of the receptor-binding domain (RBD) differ between them. Herein, we have used molecular dynamics (MD) simulations, machine lear...

Enhancement of protein thermostability by three consecutive mutations using loop-walking method and machine learning.

Scientific reports
We developed a method to improve protein thermostability, "loop-walking method". Three consecutive positions in 12 loops of Burkholderia cepacia lipase were subjected to random mutagenesis to make 12 libraries. Screening allowed us to identify L7 as ...

Deep learning the structural determinants of protein biochemical properties by comparing structural ensembles with DiffNets.

Nature communications
Understanding the structural determinants of a protein's biochemical properties, such as activity and stability, is a major challenge in biology and medicine. Comparing computer simulations of protein variants with different biochemical properties is...

Ligand-Dependent Conformational Transitions in Molecular Dynamics Trajectories of GPCRs Revealed by a New Machine Learning Rare Event Detection Protocol.

Molecules (Basel, Switzerland)
Central among the tools and approaches used for ligand discovery and design are Molecular Dynamics (MD) simulations, which follow the dynamic changes in molecular structure in response to the environmental condition, interactions with other proteins,...