AlignMe

AlignMe aligns membrane protein sequences to identify structural and evolutionary relationships among integral membrane proteins.

Key Features:

• Pairwise Sequence Alignment (PW Mode): Performs pairwise alignment of two sequences provided in FASTA format using substitution matrices, secondary structure predictions, and transmembrane propensities.
• Hydropathy Profile Alignment (HP Mode): Converts multiple sequence alignments into hydrophobicity profiles to align and compare transmembrane topologies and potential 3D folds, aiding analysis of proteins with low sequence similarity.
• Position-Specific Substitution Matrices (P): Incorporates position-specific substitution matrices to provide evolutionary context for alignments.
• Secondary structure and transmembrane predictions (S and T): Integrates secondary structure (S) and transmembrane (T) predictions to refine alignment decisions.
• Optimized parameter sets: Offers four optimized parameter sets tailored for different levels of sequence similarity to improve alignment accuracy.
• Dynamic programming with membrane-specific optimizations: Utilizes a dynamic programming algorithm enhanced for membrane proteins, including prioritization of predicted transmembrane segment matching.
• FASTA input: Accepts sequence input in FASTA format.

Scientific Applications:

• Comparative Structural Analysis: Aligning hydropathy profiles to infer structural similarities and potential folds between membrane proteins that lack significant sequence homology.
• Evolutionary Studies: Tracing evolutionary relationships among membrane proteins, including analysis of the LeuT fold and DedA domain proteins, by identifying conserved structural motifs and putative ancestral links.

Methodology:

AlignMe employs a dynamic programming algorithm enhanced by membrane-specific optimizations, including prioritization of predicted transmembrane segment matching, and uses position-specific substitution matrices together with secondary structure (S) and transmembrane (T) predictions.