title: Integrating in silico prediction methods, molecular docking, and molecular dynamics simulation to predict the impact of ALK missense mutations in structural perspective.
abstract: Over the past decade, advancements in next generation sequencing technology have placed personalized genomic medicine upon horizon. Understanding the likelihood of disease causing mutations in complex diseases as pathogenic or neutral remains as a major task and even impossible in the structural context because of its time consuming and expensive experiments. Among the various diseases causing mutations, single nucleotide polymorphisms (SNPs) play a vital role in defining individual's susceptibility to disease and drug response. Understanding the genotype-phenotype relationship through SNPs is the first and most important step in drug research and development. Detailed understanding of the effect of SNPs on patient drug response is a key factor in the establishment of personalized medicine. In this paper, we represent a computational pipeline in anaplastic lymphoma kinase (ALK) for SNP-centred study by the application of in silico prediction methods, molecular docking, and molecular dynamics simulation approaches. Combination of computational methods provides a way in understanding the impact of deleterious mutations in altering the protein drug targets and eventually leading to variable patient's drug response. We hope this rapid and cost effective pipeline will also serve as a bridge to connect the clinicians and in silico resources in tailoring treatments to the patients' specific genotype.
authors: Medical Biotechnology Division, School of Biosciences and Technology, VIT University, Vellore, Tamil Nadu 632014, India.
authors: C George Priya
authors: CG
authors: Doss
authors: Department of Bio-Informatics, School of Computer and Information Sciences, Galgotias University, India.
authors: Chiranjib
authors: 0000-0002-3958-239X
authors: C
authors: Chakraborty
authors: Key Laboratory of Systems Biology, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, China.
authors: Luonan
authors: L
authors: Chen
authors: Department of Computer Sciences, Hong Kong Baptist University, Kowloon Tong, Hong Kong.
authors: Hailong
authors: 0000-0003-0633-5525
authors: H
authors: Zhu
mesh_terms: D030301:Activin Receptors, Type II / Q000235:genetics*; D003198:Computer Simulation; D000077547:Crizotinib; D017353:Gene Deletion; D023281:Genomics; D005838:Genotype; D006801:Humans; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide; D025341:Principal Component Analysis; D011485:Protein Binding; D011720:Pyrazoles / Q000737:chemistry; D011725:Pyridines / Q000737:chemistry; D012984:Software
chemical_list: D011720:Pyrazoles; D011725:Pyridines; D000077547:Crizotinib; C425364:ACVRL1 protein, human; D030301:Activin Receptors, Type II