Theoretical-experimental studies of calmodulin-peptide interactions at different calcium equivalents

• Published in: Journal of biomolecular structure & dynamics 2022-04, Vol.40 (6), p.2689-2700
• Main Authors: Sosa-Peinado, Alejandro, León-Cruz, Erika, Velázquez-López, Isabel, Matuz-Mares, Deyamira, Cano-Sánchez, Patricia, González-Andrade, Martin
• Format: Article
• Language: English
• Subjects: and skMLCK; biosensors; calcium; calmodulin; calspermin; CaM-peptide; CaV1.1; molecular dynamic (MD); molecular modeling tools; nNOS
• ISSN: 0739-1102; 1538-0254
• DOI: 10.1080/07391102.2020.1841679

We study the CaM-peptide interactions for four CaM-related peptides with different calcium equivalents, using the hCaM-M124C-mBBr biosensor and Molecular Dynamics (MD). Due to the high sensitivity of the biosensor, we were able to calculate five K ds based on the number of calcium equivalents for each peptide, showing a directly proportional relationship between the degree of calcium saturation and the increased affinity for the Calspermin, nNOS, and skMLSK peptides; while the CaV1.1 peptide has a degree of affinity independent of the number of calcium equivalent. On the other hand, the MD studies were designed based on the experimental results; I) visualizing the effect of the gradual elimination of calcium in Holo-CaM and II) analyzing the CaM-Peptide complexes with and without calcium. We observe that the gradual addition of calcium increases the flexibility of Holo-CaM. Concerning CaM-Peptide complexes, it presents differences in both the ΔG T and the RMSD. These results demonstrate the importance of the use of biosensors and the power of MD to make inferences in systems such as CaM-peptide complexes. Communicated by Ramaswamy H. Sarma