Portland Press

Table 6

Prediction of change in structure, domain and conservation of Cyclin D1 du to missense SNP using HOPE in silico analysis

RS ID	Schematic structure	Amino acid properties	Structure	Domain (InterPro)	Conservation
rs557545630 R15S	>	The mutant residue is smaller than the WT residue, and might lead to loss of interactions. The WT residue charge was POSITIVE; the mutant residue charge is NEUTRAL, and can cause loss of interactions with other molecules or residues. The mutant residue is more hydrophobic than the WT residue, and can result in loss of hydrogen bonds and/or disturb correct folding.	No impact on structure of protein predicted	No impact on domain was predicted	The mutant residue is located near a highly conserved position and have some properties in common with WT mutated residue. This means that in some rare cases this mutation might occur without damaging the protein.
rs534553548 A190S	>	The mutant residue is bigger than the WT residue and probably will not fit in core of protein. The hydrophobicity of the WT and mutant residue differs. The mutation will cause loss of hydrophobic interactions in the core of the protein.	In the 3D-structure, it can be seen that the WT residue is located in an α-helix. The mutation converts the WT residue in a residue that does not prefer α-helices as secondary structure.	The residue is buried in the core of a domain. The differences between the WT and mutant residue might disturb the core structure of this domain.	Mutant residue is located near a highly conserved position. This mutation might occur in some rare cases, but it’s more likely that the mutation is damaging to the protein.
rs535957987 D292E	>	The WT residue charge was NEGATIVE, the mutant residue charge is NEUTRAL, which may cause loss of interactions with other molecules or residues. The mutant residue is bigger, this might lead to bumps.	No impact on structure of protein predicted.	No impact on domain was predicted.	The mutant residue was not among the other residue types observed at this position in other, homologous proteins. However, residues that have some properties in common with mutated residue were observed. This means that in some rare cases this mutation might occur without damaging the protein.
rs143479406 R179H	>	The WT residue charge was POSITIVE; the mutant residue charge is NEUTRAL. Which may cause loss of interactions with other molecules or residues. The mutant residue is smaller than the WT residue. This will cause a possible loss of external interactions.	The WT residue forms a hydrogen bond with glutamic acid at position 162 and Glutamine at position 176, and salt bridge with glutamic acid at position 162, glutamic acid at position 172. The size difference will not makes that the new residue in the correct position to make the same hydrogen bond and salt bridges.	The mutated residue is located on the surface of a domain with unknown function. The residue was not found to be in contact with other domains of which the function is known within the used structure. However, contact with other molecules or domains is still possible and might be affected by this mutation.	The mutant residue is located near a highly conserved position. Neither this mutant residue nor another residue type with similar properties was observed at this position in other homologous sequences. Based on conservation scores this mutation is probably damaging to the protein.

RS ID	Schematic structure	Amino acid properties	Structure	Domain (InterPro)	Conservation
rs557545630 R15S	>	The mutant residue is smaller than the WT residue, and might lead to loss of interactions. The WT residue charge was POSITIVE; the mutant residue charge is NEUTRAL, and can cause loss of interactions with other molecules or residues. The mutant residue is more hydrophobic than the WT residue, and can result in loss of hydrogen bonds and/or disturb correct folding.	No impact on structure of protein predicted	No impact on domain was predicted	The mutant residue is located near a highly conserved position and have some properties in common with WT mutated residue. This means that in some rare cases this mutation might occur without damaging the protein.
rs534553548 A190S	>	The mutant residue is bigger than the WT residue and probably will not fit in core of protein. The hydrophobicity of the WT and mutant residue differs. The mutation will cause loss of hydrophobic interactions in the core of the protein.	In the 3D-structure, it can be seen that the WT residue is located in an α-helix. The mutation converts the WT residue in a residue that does not prefer α-helices as secondary structure.	The residue is buried in the core of a domain. The differences between the WT and mutant residue might disturb the core structure of this domain.	Mutant residue is located near a highly conserved position. This mutation might occur in some rare cases, but it’s more likely that the mutation is damaging to the protein.
rs535957987 D292E	>	The WT residue charge was NEGATIVE, the mutant residue charge is NEUTRAL, which may cause loss of interactions with other molecules or residues. The mutant residue is bigger, this might lead to bumps.	No impact on structure of protein predicted.	No impact on domain was predicted.	The mutant residue was not among the other residue types observed at this position in other, homologous proteins. However, residues that have some properties in common with mutated residue were observed. This means that in some rare cases this mutation might occur without damaging the protein.
rs143479406 R179H	>	The WT residue charge was POSITIVE; the mutant residue charge is NEUTRAL. Which may cause loss of interactions with other molecules or residues. The mutant residue is smaller than the WT residue. This will cause a possible loss of external interactions.	The WT residue forms a hydrogen bond with glutamic acid at position 162 and Glutamine at position 176, and salt bridge with glutamic acid at position 162, glutamic acid at position 172. The size difference will not makes that the new residue in the correct position to make the same hydrogen bond and salt bridges.	The mutated residue is located on the surface of a domain with unknown function. The residue was not found to be in contact with other domains of which the function is known within the used structure. However, contact with other molecules or domains is still possible and might be affected by this mutation.	The mutant residue is located near a highly conserved position. Neither this mutant residue nor another residue type with similar properties was observed at this position in other homologous sequences. Based on conservation scores this mutation is probably damaging to the protein.