Dynamics based alignment algorithms reveal new structure-dynamics-function relations of proteins: The Hemoglobin/Myoglobin and Drosha/Dicer test cases

Sequence and structure alignment algorithms are long-standing techniques to study proteins. However, protein structures are dynamic rather than static, and understanding the relation between protein function and dynamics is fundamental for comprehending the protein structure–dynamics–function relationship. Recently, we developed novel tools to compare protein dynamics that are based on the commonly used Needleman-Wunsch and Smith-Waterman algorithms for global and local sequence alignment. Anisotropic Network Model modes of motion of the proteins are calculated and the modes are aligned using these novel algorithms. Two model systems are used to study the effect of structure on dynamics i) Hemoglobin (Hb) / Myoglobin (Mb) – globular hemeproteins with similar structure that respectively transport and store oxygen, while Mb has higher affinity for O2 than Hb; and II) Drosha / Dicer - RNase III family proteins that play a crucial role in the maturation process of micro-RNA. Low global dynamics similarity observed at both protein`s pairs, while high local dynamics similarity conservation is observed at the major exit route of the ligand (Hb and Mb) or at the catalytic domains, in the vicinity of the catalytic residues (Drosha and Dicer). The results suggest that structurally similar homologues and nonhomologous proteins can have dissimilar global dynamics, but share resemble local dynamics related to common functions. Moreover, proteins’ quaternary structure can affect the dynamics of its subunits, hence may contribute to the functional difference between proteins.