Di tiDictionary f li dof ligands

all moleculesgBank: http://www.drugbank.ca/C: http://zinc.docking.org/indexODRUG: http://www.compbio.dundeCTVS: http://www2.chemie.uni-erla

b id t t l d t b CSD htmbridge structural database - CSD: ht

cromoleculescromoleculesB: ropean EBI: http://www.ebi.ac.uk/p p

SA RSCB: http://www.rcsb.org/pSMOL (visualisation tool): http://OL (Java based visualisation tool): http

x.shtml ee.ac.uk/Web_Servers/prodrg_down.hangen.de/software/cactvs/tt // d k/ d t /ttp://www.ccdc.cam.ac.uk/products/cs

/msd/ db/download/download.do/rasmol.org/p://jmol.sourceforge.net/

Why resT tTwo atoms

Distance between atoms 1.

P

straints:id ls ideal case

3Å. B values 20 and 50

X

Chemical informdiff tdifferent re

0.88 Å

ation: Phe at two l tiesolutions

2 Å and High mobilit2 Å and High mobility

Role of r

When atoms have high B valuesolution then electron densityrestraints would not be used tould be unreasonableould be unreasonable. ole of restraints is that to retai

i d ib le same time describe electronatoms are close to each other

ave hugely different B values

restraints

s and/or data are at low y may not show separate peakthen chemistry of molecule

in chemistry of atoms and at d i i lln density optimally.it is unlikely that they will y y

Exam

a -A

Unrestrained

mple

Restrained

ard dictionary has description of arounr crystal then the will be used automat000.

happens if you have a ligand that is noibilit t t h i ll ibl dsibility to create chemically sensible d

starting to create a description you ne

2D 3D

nd 1 500 small molecules. If one of theically. In the new version there will be

ot in the dictionary. Then it is your d i tidescription.

eed to study bonding structure of your

These two molecules will refine very ydifferently (oviously)

various ke

d”

an be d using gtools. One s smile arch can bearch can be

ure

SMILES notation is the most popular notatioS o a o s e os popu a o a o

cal websites, programs use this notatioS.

sed on several simple rules. Full descht websites.www.daylight.com/dayhtml/doc/theory

S stands for Simplified Molecular InpuS s a ds o S p ed o ecu a pu

ncise and widely spread. It is very eased for manual input using text only eded for manual input using text only edrd and it is a useful thing to know abo

ESon and almost all computational o a d a os a co pu a o aon. They can read and write

cription of SMILES can be find from

y/theory.smiles.html

ut Line Entry System. u e y Sys e

sy to learn. It was originally ditors SMILES has become as aditors. SMILES has become as a out.

SMILES uses several very simple rules (thesS uses se e a e y s p e u es ( esS from structure and structure from S

c symbols used for atomsc symbols used for atomsgen atoms as a rule are implicit. Theyation about atomsbouring atoms stand one after anothe

e, double, triple and aromatic bonds arctively. Single and aromatic bonds are c e y S g e a d a o a c bo ds a ehes represented by parenthesess are added by using matching digits oatic atoms are denoted using lower caatic atoms are denoted using lower ca

rules are sufficient to describe most oles

ESse rules are sufficient to generate se u es a e su c e o ge e a eMILES).

y are deduced using valence

erre denoted using “-”, “=”, “#” and “:” usually not shown.usua y o s o

on connecting atomsasesases.

of the cases. Let us consider some

SMILE

O)C(N)Cc1ccccc1 [NH3+]

ens are implicit, aromatic and single are not shown. Stereochemistry is ar.

ExplicitStereocother s

dpresentation is not unique. Here is ILES produced by MarvinSketch:1=CC=CC=C1)C(O)=O

and caof the a

ES

][C@H](CC1=CC=CC=C1)C(O)=O

t charges are shown as an attributer of atom. chemistry is shown using @ or @@. Chirality and

stereochemical information in SMILES are local b d t d i i di t i hb h dn be understood using immediate neighbourhood

atom for which @ or @@ symbols are defined.

SMILES: atom sSMILES: atom s

s are specified using their atomic syms are specified using their atomic symet (C, N, O, S, P, F,Cl) or valency is diged then they are shown inside square

ht atom chirality charge]xamplexample - shows deuterium with atomic charg

H+] - shows positively charged nitroge+2] iron atom with atomic charge +2+2] - iron atom with atomic charge +2

ogen atoms are not usually specified. would satisfy “normal” valency of atomecified explicitly. The number of hydrodiately after hydrogen. It should not cadiately after hydrogen. It should not ca

ogens can make only one bond (excep

specificationspecification

mbol Atoms that are not in the organicmbol. Atoms that are not in the organic fferent from “normal” or are isotopes o

e brackets. General notation for atoms

e +1. n atom that is a chiral centre

In this case the number of hydrogens s is assumed. However hydrogens caogens is shown using a digit ause problem with ring closure sinceause problem with ring closure since pt in reaction intermediates).

SMILES: disconnSMILES: disconn

nsecutive atoms are not connected thensecutive atoms are not connected themple:].c1ccccc1[O-] id for.

that if a SMILES string has “.” it does ture. For example: C1.C1 is same as these atoms must be connected). ThisLES to represent reaction (e.g. reagen

nected atomsnected atoms

en between them “ ” is added Foren between them “.” is added. For

not mean that it is a disconnected CC (note that matching digits show

s notation is used in extension of nts are separated by “.”)

SMILES: stereo

k b d ith f t (om makes bond with four atoms (e.gthen we can arrange these atoms

e cannot be generated from another ugsh these two structures SMILES user an atom is specified then it means tom and the three remaining atomsom and the three remaining atomsN[C@](C)(F)C(O)=O we look down tothyl group, F and carboxyl group appe

l k iear clockwise.atom is not the first atom and it has anm. For example in case N[C@](C)C(O)p [ @]( ) ( )nd carboxyl groups appear anti-clockwn can be written explicitly.atom is the first atom then implicit hydratom is the first atom then implicit hydriral atom.

t fi d ifi ti h t h ifot find specification what happens if acit hydrogens.

ochemistry

3 b ) d ll th tg. sp3 carbon) and all these atoms ain general in two different ways. O

using rotations and translations only.g yes chirality notations - @ or @@. Ifthat if we take the first atom attachedappear anti-clockwise For exampleappear anti-clockwise. For example

o the chiral carbon from the first atomear anti-clockwise. If we write @@ th

n implicit hydrogen then it is taken as t)=O neighbours H (implicit hydrogen)) g ( p y g )wise. To avoid confusion in these case

rogen is an atom “from” where we loorogen is an atom from where we loo

hi l t i th fi t t d it ha chiral atom is the first atom and it has

Marvin

@](N)(F)C(O)=O@](N)(F)C(O)=O

nSketch

C[C@@H](O)FC[C@@H](O)F

SMILES: stereo

ration around double bonds are denotration around double bonds are denote

F ( F/C C/F) d tF (or F/C=C/F) denotesH

\C=C/

FF F (or F/C=C\F) denotes

HH \C=C/

F

at SMILES chirality and are local chira

ochemistry

ted using matching “\” and/or “/” Forted using matching \ and/or / . For

F/

C\H H

H H/

C\ F

ality.

rious info h They canThey can sed using

on tools

es

The list of compounds

3D view

PRODRGG server

JME

Load your

O GG JJME is java based program for drawing of small compounds. It

d i PRODRG2 MSD hused in PRODRG2, MSDchem

Draw your ligand,

transfer to PRODRGtransfer to PRODRG

window and run

It can write out represpin various formats suitvarious popular softwa

B is Protein Data Bank. It has all macrerimentally as well as theoretically. Thctures available in the PDB.

many cases protein structures are detempounds). These small molecular struc

0 such small molecules in the PDB.

ere are websites that allows people to all molecular compounds. These sites

romolecular structures determined here are more than 56000 macromole

ermined with some ligands (small molectures are available from PDB. There

view macromolecular structures as weare located in USA, Europe and Japa

Substructcommon exact sterexact ster

ture, segment, reoreo

Search for macromolecules and sma

OCA MSDchem

etcher is under Refinement/Restraetcheretcher.

ketch your ligand

aint Preparation/Monomer library

After regularisation

ce satisfactory dictionary has been createddel building. In refinement

d they can be used in refinement and

Your dictionary should go hereYour dictionary should go here.