SLITHER: a web server for generating contiguous conformations of substrate molecules entering into deep active sites of proteins or migrating through channels in membrane transporters.
Many proteins use a long channel to guide the substrate or ligand molecules into the well-defined active sites for catalytic reactions or for switching molecular states. In addition, substrates of membrane transporters can migrate to another side of cellular compartment by means of certain selective mechanisms. SLITHER (http://bioinfo.mc.ntu.edu.tw/slither/or http://slither.rcas.sinica.edu.tw/) is a web server that can generate contiguous conformations of a molecule along a curved tunnel inside a protein, and the binding free energy profile along the predicted channel pathway. SLITHER adopts an iterative docking scheme, which combines with a puddle-skimming procedure, i.e. repeatedly elevating the potential energies of the identified global minima, thereby determines the contiguous binding modes of substrates inside the protein. In contrast to some programs that are widely used to determine the geometric dimensions in the ion channels, SLITHER can be applied to predict whether a substrate molecule can crawl through an inner channel or a half-channel of proteins across surmountable energy barriers. Besides, SLITHER also provides the list of the pore-facing residues, which can be directly compared with many genetic diseases. Finally, the adjacent binding poses determined by SLITHER can also be used for fragment-based drug design.
Lee
Po-Hsien
PH
Division of Mechanics, Research Center for Applied Sciences, Academia Sinica, Taipei, Taiwan.
Kuo
Kuei-Ling
KL
Chu
Pei-Ying
PY
Liu
Eric M
EM
Lin
Jung-Hsin
JH
D020134:Catalytic Domain; D051272:Glucose Transporter Type 1 / Q000737:chemistry; D006801:Humans; D020407:Internet; D008024:Ligands; D026901:Membrane Transport Proteins / Q000737:chemistry*; D008958:Models, Molecular; D011487:Protein Conformation; D012984:Software; D014584:User-Computer Interface
D051272:Glucose Transporter Type 1; D008024:Ligands; D026901:Membrane Transport Proteins; C495677:SLC2A1 protein, human