MaxOcc

MaxOcc quantifies maximum occurrence (MO) by integrating SAXS and NMR data to compute the fraction of time flexible proteins spend in specific solution conformations.

Key Features:

• Conformational Space Sampling: Performs extensive sampling of protein conformational space to enable detailed analysis of conformational populations.
• MO Map Construction: Constructs maximum occurrence (MO) maps from experimental data to identify the most probable solution conformations.
• Data Integration: Integrates Small-Angle X-ray Scattering (SAXS) and Nuclear Magnetic Resonance (NMR) data, specifically pseudocontact shifts and self-orientation residual dipolar couplings derived from paramagnetic lanthanide ions.
• Case Study Validation: Validated on the flexible two-domain protein calmodulin (CaM), where SAXS and NMR showed crystalline "closed" and "fully extended" conformations with MOs of 5% and 15%, respectively, and other extended conformations with MOs up to 35%.
• Universal Applicability: Applicable to diverse proteins using standard SAXS data and specific NMR data on lanthanide derivatives obtained via native metal sites or lanthanide tagging.

Scientific Applications:

• Quantification of Solution Populations: Determines the fraction of time flexible proteins occupy specific conformations in solution using MO values.
• Structural and Functional Interpretation: Informs understanding of protein function and interactions by identifying prevalent conformations under native-like conditions.
• Support for Structural Biology, Biochemistry, and Drug Design: Provides population-weighted conformational information relevant to mechanistic studies and ligand design.

Methodology:

Performs extensive conformational space sampling, constructs MO maps from experimental data, and integrates SAXS with NMR pseudocontact shifts and self-orientation residual dipolar couplings derived from paramagnetic lanthanide ions.