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Superpositions and alignments in YASARA

In addition to a classical superposition that minimizes the RMSD between two atom selections, YASARA supports a number of special features:

Superposition and alignment
Figure 1: Superposition and alignment
  • Chemically equivalent atoms can be flipped automatically to minimize the RMSD. For example when calculating the heavy-atom RMSD between two proteins, it may happen that a certain Phe side-chain has been flipped by 180 degrees, i.e. the CD1/CE1 atoms have swapped place with CD2/CE2. Chemically the result is identical, yet a wrong RMSD will be calculated if the atoms are not flipped back. YASARA supports this flipping for all kinds of molecules by analyzing the structure to search for equivalent atoms to flip (YASARA View+).
  • Simultaneous superposition of multiple objects on their core regions. When calculating an NMR structure, it is usually needed to superpose the resulting bundle of structures all together, putting most emphasis on the core regions, so that the superposition is not negatively influenced by floppy tails. To achieve this goal, YASARA features the THESEUS maximum likelihood method[1] (YASARA View+).
  • Structural alignments. If it is not known which atoms should actually be superposed, one needs to create an alignment first. When working with proteins, the most successful approach is to ignore the sequence and concentrate on the structure only. This allows to superpose also distantly related proteins with high accuracy. A large number structural alignment programs have been developed. YASARA has a built-in MUSTANG module[2] and a local plugin for SHEBA[3] in Linux and MacOS (YASARA View+).
  • Twisted structural alignments. YASARA can bend and wind proteins to maximize the number of structurally aligned residues, for example to create sequence profiles for homology modeling (YASARA Structure).
  • Structural alignments of small molecules. YASARA Model and above can automatically locate the largest common substructure of small molecules like ligands and superpose them. YASARA Dynamics and above can additionally perform a gradient-based optimization of the alignment, i.e. they can bend and twist the small molecule to move similar functional groups on top of each other and increase the number of aligned atoms. Various similarity scores like the LS-Score and PC-Score[4] are calculated and returned (YASARA Model+, minimization requires YASARA Dynamics+).
  • Multiple structural alignments. If the goal is to align and superpose an entire protein family, the required multiple structural alignment can be performed with the built-in MUSTANG module[2] (YASARA View+).
  • Sequence alignments. In some rare applications, one needs to superpose proteins based on a sequence alignment. YASARA supports local Smith&Waterman and global Needleman&Wunsch sequence alignments to achieve this goal (YASARA View+).

R E F E R E N C E S

[1] THESEUS: maximum likelihood superpositioning and analysis of macromolecular structures
Theobald DL, Wuttke DS (2006) Bioinformatics 22, 2171-2172
[2] MUSTANG: A multiple structural alignment algorithm
Konagurthu AS, Whisstock JC, Stuckey PJ, Lesk AM (2006) Proteins 64, 559-574
[3] Protein structure alignment using environmental profiles
J.Jung & B.Lee, (2000) Protein Eng. 13, 535-543
[4] LS-align: an atom-level, flexible ligand structural alignment algorithm for high-throughput virtual screening
Hu J, Liu Z, Yu DJ, Zhang Y (2018) Bioinformatics 34, 2209-2218