In order to use these libraries for production of topology and coordinate files to be further used for AMBER simulations do the following in tleap or xleap:

 

Source GLYCAM06 force field: source $AMBERHOME/dat/leap/cmd/leaprc.GLYCAM_06j-1

Load the library (LIB.lib) you need: loadoff LIB.lib

Now you can either use sequence command to build your GAG: new_unit=sequence { … LIB …}

Or you can read the data from the pdb, where the residues are already renamed to be compatible with the nomenclature of the libraries:new_unit=loadpdb my_pdb_which_includes_residue_LIB.pdb

 

Be careful with Ido2UA residues: if you want to build a heparin molecule or a molecule, which contains Ido2UA, pay attention to the fact that this residue rather exists in 1C4 and 2S0 conformations. In our libraries, however, ALL the residues are in 4C1 conformation. Therefore, DO NOT use sequence command to build your GAG. Instead you can use these two prepared files with heparin dp10 with Ido2SUA in 1C4 and 2S0 conformations and read them by loadpdb command. These structures originate from the experimental structure (PDB ID: 1HPN) and contain already renamed residues/atoms to be compatible with our libraries. If you use an experimental structure of a protein complex with heparin, just rename the residues according to the nomenclature in our libraries and read them in. The same applies to the residues, for which you know that their conformations are not 4C1.

 

1. Case DA, Berryman JT, Betz RM, Cerutti DS, Cheatham TE, Darden TA, Duke RE, Giese TJ, Gohlke H, Goetz AW, Homeyer N, Izadi S, Janowski P, Kaus J, Kovalenko A, Lee TS, LeGrand S, Li P, Luchko T, Luo R, Madej B, Merz KM, Monard G, Needham P, Nguyen H, Nguyen HT, Omelyan I, Onufriev A, Roe DR, Roitberg A, Salomon-Ferrer R, Simmerling CL, Smith W, Swails J, Walker RC, Wang J, Wolf RM, Wu X, York DM, Kollman PA. AMBER 14. San Francisco: University of California; 2015.

2. Kirschner K, Yongye A, Tschampel S, González-Outeiriño J, DaNon-terminalls C, Foley L, Woods R. GLYCAM06: a generalizable biomolecular force field. carbohydrates. J. Comput. Chem. 2008;29:622–655.

3. Huige C, Altona C. Force field parameters for sulfates and sulfamates based on Ab initio calculations: extensions of AMBER and CHARMm Fields. J. Comput. Chem. 1995;16:56–79.

 

AMBER library

(residue name)

 

Chemical formula

 

 

Terminal

/non-terminal

 

Carbon participating

in glycosidic linkage

 

Sulfation pattern

 

 

01Gα-D-Glc(2S,3S,6S)Terminal2S, 3S, 6S
02uα-L-IdoA(2S)Terminal2S
02Yα-D-Glc(NS)TerminalNS
02Zβ-D-GlcA(2S)Terminal2S
03uα-L-IdoA(3S)Terminal3S
03Zβ-D-GlcA(3S)Terminal3S
04Bβ-D-GlcNAc(4S)Terminal4S
04Vβ-D-GalNAc(4S)Terminal4S
04Yα-D-GlcNAc(4S)Terminal4S
06Bα-D-GlcNAc(6S)Terminal6S
06Lβ-D-Gal(6S)Terminal6S
06Vβ-D-GalNAc(6S)Terminal6S
06Yα-D-GlcNAc(6S)Terminal6S
07Bα-D-GlcNAc(4S,6S)Terminal4S,6S
07uα-L-IdoA(2S,3S)Terminal2S,3S
07Vβ-D-GalNAc(4S,6S)Terminal4S,6S
07Yα-D-Glc(6S,NS)Terminal6S,NS
07Zβ-D-GlcA(2S,3S)Terminal2S,3S
08Gα-D-Glc(2S,6S)Terminal2S,6S
09Gα-D-Glc(3S,6S)Terminal3S,6S
S7Zβ-D-GlcA(2S,3S,4S)Terminal2S,3S,4S
34Bβ-D-GlcNAc(4S)Non-Terminal34S
34Vβ-D-GalNAc(4S)Non-Terminal34S
36Bα-D-GlcNAc(6S)Non-Terminal36S
36Lβ-D-Gal(6S)Non-Terminal36S
36Vβ-D-GalNAc(6S)Non-Terminal36S
36Yα-D-GlcNAc(6S)Non-Terminal36S
37Bβ-D-GlcNAc(4S,6S)Non-Terminal34S,6S
37Vβ-D-GalNAc(4S,6S)Non-Terminal34S,6S
39Yα-D-GlcNAc(4S,6S)Non-Terminal34S,6S
41Gβ-D-Glc(2S,3S,6S)Non-Terminal42S,3S,6S
42uα-L-IdoA(2S)Non-Terminal42S
42Yα-D-Glc(NS)Non-Terminal4NS
42Zβ-D-GlcA(2S)Non-Terminal42S
43uα-L-IdoA(3S)Non-Terminal43S
43Zα-D-GlcA(3S)Non-Terminal43S
46Vβ-D-GalNAc(6S)Non-Terminal46S
46Yα-D-GlcNAc(6S)Non-Terminal46S
47uα-L-IdoA(2S,3S)Non-Terminal42S,3S
47Yα-D-Glc(6S,NS)Non-Terminal46S,NS
47Zβ-D-GlcA(2S,3S)Non-Terminal43S,3S
48Gα-D-Glc(2S,6S)Non-Terminal42S,6S
49Gα-D-Glc(3S,6S)Non-Terminal43S,6S
46Bα-D-GlcNAc(6S)Non-Terminal46S
49Yα-D-Glc(2S,6S,NS)Non-Terminal42S,6S,NS
ROSSO3Non-Terminal42S,6S,NS

Docking GAGs with Autodock 3

Here are the GAG ligands prepared to be docked by AD3. The charges are assigned with the use of the GLYCAM06-compatible libraries accessible above.

Abbreviations:
HE: heparin (1C4 conformation of IduA(2SO))
DS: dermatan sulfate
CS: chondroitin sulfate
HA: hyaluronic acid
deHE: desulfated heparin (a variant of heparan sulfate)
pHA: persulfated hyaluronic acid
dp: degree of polymerization
octa, hexa, tetra, di: octamers, hexamers, tetramers, dimers

The numbers after the GAG abbreviation relate to the sulfation pattern (positions of the sulfates: first numbers correspond to the N-monosaccharide monosaccharide unit, the next ones to the uronic acid monosaccharide unit; to be sure, check the structures since, for example, HA2 relates to thesulfate in the seond position of the uronic acid monosaccharide unit).

In our AD3 protocol we usually obtain 1000 solutions that are further clustered and analyzed. In comparison to the default parameters, the following ones are modified:

ga_pop_size 300 # number of individuals in population
ga_num_evals 999500000 # maximum number of energy evaluations
ga_num_generations 10000 # maximum number of generations

Biomolecular modelling: methodology and case studies in computational biology

Lecture1 Introduction to the course. Force field. Docking.

Lecture2 Molecular dynamics (MD).

Lecture3 Solvent in biomolecular modelling.

Lecture4 Protein folding.

Lecture5 Computational glycobiology.

Lecture6 Basics of QM.

Lecture7 MD, QM and NMR.

Introduction to Molecular and Cellular Biology

Lecture1Lecture2Lecture3-4Lecture5-6 Introduction to cell chemistry and biosynthesis.

Lecture7-8Lecture9Lecture10-11 Cell organization.

Lecture12-13 Cellular nucleus.

Lecture14-16. Cell membrane.

Lecture17-18 Vesicular transport.

Lecture19-20 Cellular signaling.

Lecture21-22Lecture23-24 Cell cycle.

Lecture25-26 Cell junctions and adhesion.