Example Case

Human KRAS G12C (PDB: 6OIM)

Input Info
PDB: 6OIM_A
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Status
Completed
Duration: 12.5s
Downloads
Results Available
3D Visualization & Details
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Protein Sequence
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Covalent Pocket Details
Residue Index Type Confidence
VAL 10 Binding Site 0.994
GLY 11 Binding Site 0.992
ALA 12 Binding Site 0.990
CYS 13 Reaction Site 0.993
GLY 14 Binding Site 0.960
LYS 17 Binding Site 0.905
PRO 35 Binding Site 0.993
THR 59 Binding Site 0.995
ALA 60 Binding Site 0.944
GLY 61 Binding Site 0.994
GLN 62 Binding Site 0.997
GLU 63 Binding Site 0.986
GLU 64 Binding Site 0.919
TYR 65 Binding Site 0.722
ARG 69 Binding Site 0.987
ASP 70 Binding Site 0.889
TYR 72 Binding Site 0.738
MET 73 Binding Site 0.993
PHE 79 Binding Site 0.650
HIS 96 Binding Site 0.784
TYR 97 Binding Site 0.995
GLN 100 Binding Site 0.987
ILE 101 Binding Site 0.981
ARG 103 Binding Site 0.621
VAL 104 Binding Site 0.951
Protein & Pocket Properties
Sequence Length
167 residues
Molecular Weight
19.00 kDa
Total SASA
9120.16 Ų
Pocket Volume
2160.08 ų
Area: 936.76 Ų
Hydrophobicity
-0.69
Hydrophilic
Electrostatics
0.1 Net Charge
Reactive Residue
Residue Index Residue Name QSASA pKa
13 CYS 76.71% 9.01
Suggested Warheads
CYS
Targeting Cysteine
Michael Addition

Irreversible covalent bond formation via nucleophilic attack on an α,β-unsaturated carbonyl system.

Michael Addition
Leads to
Recommended Warheads
Acrylamide
Acrylamide
Acrylate
Acrylate
α,β-unsaturated Carbonyl
α,β-unsaturated Carbonyl
α-cyanovinyl Carbonyl
α-cyanovinyl Carbonyl
Vinyl Sulfone
Vinyl Sulfone
Vinyl Sulfonamide
Vinyl Sulfonamide
Butadienyl Carbonyl
Butadienyl Carbonyl
Conjugated System
Conjugated System
Propynamide
Propynamide
Vinyl Sulfonate
Vinyl Sulfonate
Mannich Base
Mannich Base
Nitroalkene
Nitroalkene
β-sulfonylvinyl Carbonyl
β-sulfonylvinyl Carbonyl
β-sulfonylvinyl Nitrile
β-sulfonylvinyl Nitrile
Hemi(thio)acetalization

Reversible addition of nucleophiles to electrophilic carbonyls.

Hemi(thio)acetalization
Leads to
Recommended Warheads
Aldehyde
Aldehyde
α-ketoamide
α-ketoamide
Ketone
Ketone
α-hydroxy Sulfonic Acid
α-hydroxy Sulfonic Acid
Aldehyde Adduct
Aldehyde Adduct
Ubiquitin Aldehyde
Ubiquitin Aldehyde
Nucleophilic Aliphatic Substitution

Displacement of a leaving group on an aliphatic carbon.

Nucleophilic Aliphatic Substitution
Leads to
Recommended Warheads
Haloacetamide
Haloacetamide
α-halomethyl Ketone
α-halomethyl Ketone
α-acyloxymethyl Ketone
α-acyloxymethyl Ketone
Alkyl Halide
Alkyl Halide
Haloacetamidine
Haloacetamidine
α-diazomethyl Ketone
α-diazomethyl Ketone
α-aryloxymethyl Ketone
α-aryloxymethyl Ketone
α-haloamide
α-haloamide
α-halocarboxylate
α-halocarboxylate
Disulfide Formation

Reversible formation of disulfide bonds via exchange with activated disulfides.

Disulfide Formation
Leads to
Recommended Warheads
Disulfide
Disulfide
Thiol
Thiol
Thiosulfonate
Thiosulfonate
Isothiazolinone
Isothiazolinone
Oxycarbonyl-disulfide
Oxycarbonyl-disulfide
Nucleophilic Addition to a Triple Bond

Addition of nucleophile across a carbon-carbon or carbon-heteroatom triple bond.

Nucleophilic Addition to a Triple Bond
Leads to
Recommended Warheads
Nitrile
Nitrile
Azanitrile
Azanitrile
Alkyne
Alkyne
Epoxide Opening

Ring opening of strained epoxide rings by nucleophilic attack.

Epoxide Opening
Leads to
Recommended Warheads
Epoxide
Epoxide
Nucleophilic Aromatic Substitution

Displacement of a leaving group on an aromatic ring.

Nucleophilic Aromatic Substitution
Leads to
Recommended Warheads
Aryl Halide
Aryl Halide
Aryl Sulfone
Aryl Sulfone
Nitroarene
Nitroarene
Nucleophilic Acyl Substitution

Substitution at an acyl group, often involving activated esters or carbamates.

Nucleophilic Acyl Substitution
Leads to
Recommended Warheads
Ester
Ester
Thioester
Thioester
Acylphosphonate
Acylphosphonate
Beta-Lactam Addition

Nucleophilic attack on the beta-lactam ring resulting in ring opening and acylation.

Beta-Lactam Addition
Leads to
Recommended Warheads
β-lactam
β-lactam
Lactone Addition

Nucleophilic attack on lactone rings leading to ring opening.

Lactone Addition
Leads to
Recommended Warheads
γ-lactone
γ-lactone
β-lactone
β-lactone
Aziridine Opening

Ring opening of aziridine rings by nucleophilic attack.

Aziridine Opening
Leads to
Recommended Warheads
Aziridine
Aziridine
Others

Other miscellaneous mechanisms.

Recommended Warheads
Urea
Urea
Uridine
Uridine
α-amino Carbonyl
α-amino Carbonyl
Carboxylic Acid
Carboxylic Acid
Amidine
Amidine
Catechol
Catechol
Enamine
Enamine
Nitroso
Nitroso
Alkenyl Halide
Alkenyl Halide
Azo
Azo
Cyclopropane
Cyclopropane
Haloisoxazoline
Haloisoxazoline
Hydrazide
Hydrazide
Isocyanide
Isocyanide
Isothiocyanate
Isothiocyanate
Purine
Purine
Sulfoxide
Sulfoxide
Thioether
Thioether