FastRelaxMover parameters for antibody-antigen interaction analysis

[Anonymous]

Greetings,

I am fairly new to Rosetta so please apologize if the questions I am having are fairly surface level. My project aims to analyze different antigen-antibody crystal structures to make predictions if different mutations of the antigen would influence binding. Therefore I am currently inputting crystal structures, using the FastRelaxMover and afterward analyzing them using the InterfaceAnalyzerMover. Currently, I am working with an XML script that I obtained from a student who was working on a similar project before. The XML script was written to accept two protein chains A and B as input and perform docking/design.

Since I am working with antibodies and would like to use the AntibodyDesignMover at some point I adapted the XML script so AHo numbered antibodies are accepted. The script still seems to work out fine but I am unsure if the definition of the FastRelaxMover is still adequate for the new format. I’ve been having trouble getting my head around the whole foldtree concept to which the jump definition is connected. The structures that I am inputting are always of the format: Antigen + heavy chain + light chain (in this order). I am confused about what is achieved by the movemap and the definition jump = 1 and sadly my predecessor wasn’t able to explain it either. Does jump = 1 still fit when I am working with three instead of two chains or do I have to redefine the foldtree in some way? Below you can find the FastRelaxMover I am using as well as all parameters which are defined in it. I would be thankful for any help! 

 

<TASKOPERATIONS>

        # Set lazy memory Interaction Graph

        <SetIGType name="lazymem" lazy_ig="true"/>



        # Prevents chi 2 rotamers far from 90 degree of aromatic residues

        <LimitAromaChi2 name="limitchi" chi2max="110" chi2min="70" include_trp="True" />



        # During packing, increase sampling by using extra rotamers

        <ExtraRotamersGeneric name="ex1_ex2" ex1="1" ex2aro="1" />

        <ExtraRotamersGeneric name="ex1" ex1="1" />



        # Only Design Positions and pack interface region

        # 1. defines the aa which can be used for design

        # 2. positions in the interface but not with the right orientation and distance are

# restricted to be repacked

        # 3. postions which are not in the interface are prevented from repacking

        <DesignRestrictions name="f_design">

            <Action residue_selector="positions_LH" aas="ADEFGHIKLMNPQRSTVWY"/>

            <Action residue_selector="not_positions_LH"

residue_level_operations="RestrictToRepacking"/>

            <Action residue_selector="rest" residue_level_operations="PreventRepacking"/>

        </DesignRestrictions>



 </TASKOPERATIONS>



<MOVE_MAP_FACTORIES>

        # movemap contorls the minimizer

        # 1. allows side chain (chi) movement but no backbone (bb) movement

        # 2. allow backbone movement for interface region

        <MoveMapFactory name="bbforinterface" bb="0" chi="1">

            <Backbone residue_selector="interface"/>

        </MoveMapFactory>

</MOVE_MAP_FACTORIES>



<MOVERS>

        # Fast Relax protocol using previously defined taskoperations and movemaps

        <FastRelax name="FastRelax" repeats="1" min_type="dfpmin_armijo_nonmonotone"

task_operations="limitchi,f_design,lazymem,ex1_ex2" movemap_factory="bbforinterface">

            <MoveMap name="MM" >

                <Jump number="1" setting="true" />

            </MoveMap>

        </FastRelax>



<MOVERS>

 

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