M4T

M4T performs comparative protein structure modeling by selecting and combining multiple template structures and refining sequence-to-structure alignments to improve model accuracy, particularly at low sequence identity.

Key Features:

• Multiple Templates (MT) Module: Selects and optimally combines sequences from multiple template structures using an iterative clustering approach that evaluates each template's unique contribution.
• Template contribution evaluation: Considers sequence similarity to other templates and to the target sequence and the quality of experimental resolution when assessing templates.
• Multiple Mapping Method (MMM) Module: Refines sequence-to-structure alignment accuracy by integrating inputs from three profile-to-profile-based alignment methods and iteratively comparing and ranking alternative aligned regions based on structural compatibility with templates.
• Low sequence identity refinement: Improves alignment fidelity and model precision at lower sequence identity levels where traditional methods may falter.
• Performance benchmarking: Evaluated against CASP6 comparative modeling targets and a larger independent test set and reported to perform favorably relative to contemporary methods.

Scientific Applications:

• Comparative protein structure modeling: Predicts three-dimensional protein structures by leveraging homologous template information.
• Low-identity structure prediction: Enables structure prediction for targets with low sequence identity to known templates through enhanced alignment and template combination.
• Functional and evolutionary inference: Facilitates interpretation of protein function, interaction networks, and evolutionary relationships from derived structural models.

Methodology:

Template selection employs iterative clustering to evaluate each template's unique contribution based on sequence similarity to other templates and the target and experimental resolution; alignment refinement integrates three profile-to-profile alignment methods and iteratively compares and ranks alternative aligned regions by structural compatibility with the template structures.