Table 1.
List of nsSNPs present in CDK4 gene and their predicted SIFT, PolyPhen2 and I-Mutant3 scores.
Fig 1.
CDK4 (Yellow) in complex with CyclinD1 (Orange) protein and all the five highly deleterious variants are highlighted in stick model (Green colour).
Table 2.
Binding energies of CDK4 native and mutant proteins with drug flavopiridol.
Table 3.
List of virtually selected compounds similar to flavopiridol from DrugBank database.
Table 4.
Virtual compounds with highest binding energy with CDK4 mutant proteins.
Fig 2.
Ligplot analysis of CDK4 mutant proteins with virtual compounds.
(A) Ligplot showing interaction between mutant type R24C and 5_7_DIHYDROXY_2_ (3_4_5_TRIHYDROXYPHENYL) _4H_CHROMEN_4_ONE. (B) Ligplot showing interaction between mutant model Y180H and Diosmin. (C) Ligplot showing interaction between mutant type A205T and Rutin. (D) Ligplot showing interaction between mutant type R210P and Rutin. (E) Ligplot showing interaction between mutant type R246C and 5_7_DIHYDROXY_2_ (3_4_5_TRIHYDROXYPHENYL) _4H_CHROMEN_4_ONE.
Fig 3.
Total number of hydrogen bond formed between CDK4 and cyclin D1 protein in native and mutant state.
Black, Red, Green, Blue, Orange and Pink lines indicate native, R24C, Y180H, A205T, R210P and R246C protein complexes respectively.
Fig 4.
Minimum distance between CDK4 and cyclin D1 protein in native and mutant state.
Black, Red, Green, Blue, Orange and Pink lines indicate native, R24C, Y180H, A205T, R210P and R246C protein complexes respectively.
Fig 5.
Total number of hydrogen bond formed between CDK4 and different inhibitors in native and mutant state.
Black, Red, Green, Blue, Orange and Pink lines indicate the hydrogen bonds formed between CDK4-flavopiridol, R24C-5_7_DIHYDROXY_ 2_ (3_4_5_TRI HYDRO XYPHENYL) _4H_CHROMEN_ 4_ONE, Y180H-Diosmin, A205T-Rutin, R210P-Rutin and R246C-5_7_DIHYDROXY_2_ (3_4_5_TRIHYDROXYPHENYL) _4H_CHROMEN_ 4_ONE respectively.
Fig 6.
Minimum distance between CDK4 and different inhibitors in native and mutant state.
Black, Red, Green, Blue, Orange and Pink lines indicate the hydrogen bonds formed between CDK4-flavopiridol, R24C-5_7_DIHYDROXY_ 2_ (3_4_5_TRI HYDRO XYPHENYL) _4H_CHROMEN_ 4_ONE, Y180H-Diosmin, A205T-Rutin, R210P-Rutin and R246C-5_7_DIHYDROXY_2_ (3_4_5_TRIHYDROXYPHENYL) _4H_CHROMEN_ 4_ONE respectively.