KOSMOS

KOSMOS performs harmonic and anharmonic analyses of macromolecular structures (DNA, RNA, proteins and complexes such as ribosomes) to compute vibrational modes, B-factors, and plausible conformational transition pathways.

Key Features:

• Harmonic Analysis (NMA/ENM): Implements normal mode analysis (NMA) based on elastic network models (ENMs) to calculate vibrational modes and B-factors for structural and functional insight.
• Anharmonic Analysis (ENI): Uses elastic network interpolation (ENI) to generate transition pathways between two specified conformations by optimizing a topology-oriented cost function that avoids steric clashes.
• Pathway Quality Assessment: Evaluates computed pathways based on topology, energy cost, and compatibility with NMA results.
• Coarse-Graining Options: Supports ENMs ranging from full-atom to coarse-grained, backbone, and hybrid models to vary degrees of freedom.
• ENM Connection Rules: Employs distance-cutoff, number-cutoff, and chemical-cutoff connection rules within the ENM framework.
• Input Formats: Accepts PDB identifiers and PDB-format structural files as inputs for analyses.
• Data Management: Stores simulation outputs in NMA and ENI databases.

Scientific Applications:

• Thermal fluctuation analysis: Characterizes thermal fluctuations and vibrational behavior of DNA, RNA, proteins, and complexes via NMA-derived B-factors and modes.
• Conformational transition modeling: Generates and assesses plausible transition pathways between conformations to study structural rearrangements and avoid steric clashes.
• Multi-scale dynamics of large assemblies: Applies full-atom to coarse-grained ENMs to investigate dynamics of large macromolecular assemblies such as ribosomes.

Methodology:

Performs normal mode analysis (NMA) using elastic network models (ENMs) to compute vibrational modes and B-factors; performs elastic network interpolation (ENI) to generate transition pathways between two specified conformations by optimizing a topology-oriented cost function that avoids steric clashes; assesses pathway quality by topology, energy cost, and compatibility with NMA; supports ENMs from full-atom to coarse-grained/backbone/hybrid and connection rules (distance-cutoff, number-cutoff, chemical-cutoff); stores outputs in NMA and ENI databases.