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Basic Characteristics of Mutations
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Mutation Site
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T97A |
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Mutation Site Sentence
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The molecular docking scores obtained for various mutation models like 3 individual accessory mutations (L74M, T97A and G163R), major mutation (Q148H, N155H) and also in combination of accessory (L74M, T97A and G163R), accessory and major mutations (L74M, T97A, G163R and Q148H), (L74M, T97A, G163R and N155H) were compared with wild type strain. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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IN |
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Standardized Encoding Gene
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gag-pol:155348
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Genotype/Subtype
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HIV-1 |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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HIV Infections
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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Y |
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Treatment
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INSTIs |
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Location
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India |
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Literature Information
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PMID
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28149058
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Title
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Effect of HIV-1 Subtype C integrase mutations implied using molecular modeling and docking data
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Author
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Sachithanandham J,Konda Reddy K,Solomon K,David S,Kumar Singh S,Vadhini Ramalingam V,Alexander Pulimood S,Cherian Abraham O,Rupali P,Sridharan G,Kannangai R
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Journal
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Bioinformation
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Journal Info
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2016 Jun 15;12(3):221-230
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Abstract
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The degree of sequence variation in HIV-1 integrase genes among infected patients and their impact on clinical response to Anti retroviral therapy (ART) is of interest. Therefore, we collected plasma samples from 161 HIV-1 infected individuals for subsequent integrase gene amplification (1087 bp). Thus, 102 complete integrase gene sequences identified as HIV-1 subtype-C was assembled. This sequence data was further used for sequence analysis and multiple sequence alignment (MSA) to assess position specific frequency of mutations within pol gene among infected individuals. We also used biophysical geometric optimization technique based molecular modeling and docking (Schrodinger suite) methods to infer differential function caused by position specific sequence mutations towards improved inhibitor selection. We thus identified accessory mutations (usually reduce susceptibility) leading to the resistance of some known integrase inhibitors in 14% of sequences in this data set. The Stanford HIV-1 drug resistance database provided complementary information on integrase resistance mutations to deduce molecular basis for such observation. Modeling and docking analysis show reduced binding by mutants for known compounds. The predicted binding values further reduced for models with combination of mutations among subtype C clinical strains. Thus, the molecular basis implied for the consequence of mutations in different variants of integrase genes of HIV-1 subtype C clinical strains from South India is reported. This data finds utility in the design, modification and development of a representative yet an improved inhibitor for HIV-1 integrase.
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Sequence Data
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KF870715-KF870774;KF870776-KF870797;KF870801;KF870805-KF870813;KF870816;KF870822-KF870826;KF870829-KF870832
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