Protein loops with multiple meta-stable conformations: a challenge for sampling and scoring methods

Amélie Barozet (1) , Marc Bianciotto (2) , Marc Vaisset (3) , Thierry Simeon (1) , Hervé Minoux (2) , Juan Cortés (1)

1 LAAS-RIS - Équipe Robotique et InteractionS
2 Sanofi [Vitry-sur-Seine]
3 LAAS-IDEA - Service Informatique : Développement, Exploitation et Assistance

Flexible regions in proteins, such as loops, cannot be represented by a single conformation. Instead, conformational ensembles are needed to provide a more global picture. In this context, identifying statistically meaningful conforma-tions within an ensemble generated by loop sampling techniques remains an open problem. The difficulty is primarily related to the lack of structural data about these flexible regions. With the majority of structural data coming from X-ray crystallography and ignoring plasticity, the conception and evaluation of loop scoring methods is challenging. In this work, we compare the performance of various scoring methods on a set of 8 protein loops that are known to be flexible. The ability of each method to identify and select all of the known conformations is assessed, and the underlying energy landscapes are produced and projected to visualize the qualitative differences obtained when using the methods. Statistical potentials are found to provide considerable reliability despite their being designed to tradeoff accuracy

Mots clés: Abbreviations: PCA; Principal Component Analysis; PDB; Protein Data Bank; RMSD; Root-Mean-Squared Deviation

Domaines: Biotechnologie; Biologie structurale [q-bio.BM]; Bio-Informatique, Biologie Systémique [q-bio.QM]

Amélie Barozet, Marc Bianciotto, Marc Vaisset, Thierry Simeon, Hervé Minoux, et al.. Protein loops with multiple meta-stable conformations: a challenge for sampling and scoring methods. Proteins - Structure, Function and Bioinformatics, 2021, 89 (2), pp.218-231. ⟨10.1002/prot.26008⟩. ⟨hal-02947409⟩