Create nem Class interaction (Amide-π Stacking)

[pablo-arantes]

Hi All,

Thank you for the work you have done on Prolif library. It's a great resource and help a lot of scientists in the field.
At our group we are trying to implement a new type of interaction, similar to π-π stacking, however it's an amide of the protein backbone and the aromatic ring. We have created new classes, as you can check above:

class AmideFaceToFace(BasePiStacking):
    """Face-to-face Amide-Pi Stacking interaction between a ligand (amide) and a residue (aromatic ring)

    Parameters
    ----------
    amide : str
        SMARTS pattern for the amide group
    pi_ring : tuple
        SMARTS for aromatic rings
    distance : float
        Cutoff distance between the amide and ring centroids
    plane_angle : tuple
        Min and max values for the angle between the planes
    normal_to_centroid_angle : tuple
        Min and max angles allowed between the vector normal to the ring's plane,
        and the vector between the centroids.
    """

    def __init__(
        self,
        amide: str = "[NX3][CX3](=[OX1])[#6]",
        pi_ring: tuple[str, ...] = (
            "[a;r6]1:[a;r6]:[a;r6]:[a;r6]:[a;r6]:[a;r6]:1",
            "[a;r5]1:[a;r5]:[a;r5]:[a;r5]:[a;r5]:1",
        ),
        distance: float = 5.5,
        plane_angle: "Angles" = (0, 35),
        normal_to_centroid_angle: "Angles" = (0, 33),
    ) -> None:
        super().__init__(
            lig_pattern=amide,
            prot_pattern=pi_ring,
            distance=distance,
            plane_angle=plane_angle,
            normal_to_centroid_angle=normal_to_centroid_angle,
        )


class AmideEdgeToFace(BasePiStacking):
    """Edge-to-face Amide-Pi Stacking interaction between a ligand (amide) and a residue (aromatic ring)

    Parameters
    ----------
    amide : str
        SMARTS pattern for the amide group
    pi_ring : tuple
        SMARTS for aromatic rings
    distance : float
        Cutoff distance between the amide and ring centroids
    plane_angle : tuple
        Min and max values for the angle between the planes
    normal_to_centroid_angle : tuple
        Min and max angles allowed between the vector normal to the ring's plane,
        and the vector between the centroids.
    intersect_radius : float
        Used to check whether the intersect point between planes falls within
        ``intersect_radius`` of the opposite centroid.
    """

    def __init__(
        self,
        amide: str = "[NX3][CX3](=[OX1])[#6]",
        pi_ring: tuple[str, ...] = (
            "[a;r6]1:[a;r6]:[a;r6]:[a;r6]:[a;r6]:[a;r6]:1",
            "[a;r5]1:[a;r5]:[a;r5]:[a;r5]:[a;r5]:1",
        ),
        distance: float = 6.5,
        plane_angle: "Angles" = (50, 90),
        normal_to_centroid_angle: "Angles" = (0, 30),
        intersect_radius: float = 1.5,
    ) -> None:
        super().__init__(
            lig_pattern=amide,
            prot_pattern=pi_ring,
            distance=distance,
            plane_angle=plane_angle,
            normal_to_centroid_angle=normal_to_centroid_angle,
            intersect=True,
            intersect_radius=intersect_radius,
        )


class AmidePiStacking(Interaction):
    """Amide-Pi Stacking interaction between a ligand (amide) and a residue (aromatic ring)

    Parameters
    ----------
    ftf_kwargs : dict
        Parameters to pass to the underlying AmideFaceToFace class
    etf_kwargs : dict
        Parameters to pass to the underlying AmideEdgeToFace class
    """

    def __init__(
        self, ftf_kwargs: dict | None = None, etf_kwargs: dict | None = None
    ) -> None:
        self.ftf = AmideFaceToFace(**ftf_kwargs or {})
        self.etf = AmideEdgeToFace(**etf_kwargs or {})

    def detect(
        self, ligand: "Residue", residue: "Residue"
    ) -> Iterator["InteractionMetadata"]:
        yield from self.ftf.detect(ligand, residue)
        yield from self.etf.detect(ligand, residue)

Can you please let me know if we are in the right track, and we can move on and implement?

Again, thank you so much.

Best,

Pablo

[cbouy]

Hi @pablo-arantes and thanks a lot for the praise, it's really appreciated 🙌
Also sorry for taking so long to reply 😅

So the problem with the BasePiStacking class that you're inheriting from is that it doesn't have a lig_pattern/prot_pattern like the other classes, it only has a single pi_ring that is matched in pairs against both the ligand and protein, so wouldn't work for that (you'd end up with amide-amide and ring-ring pairs).

It sounds like CationPi is a better fit for what you're trying to implement, although it only has a distance between the first atom in the cation pattern and the ring centroid, as well as an angle between the vector normal to the ring plane and the vector between the centroid and the first cation atom. You'll probably need to add another angle check on top of that to distinguish between the "edge to face" and "face to face" cases if these are relevant for this interaction, something like:

class ArHN(PiCation):
    """Interaction between a ligand (aromatic ring) and residue (backbone amide)"""
    def __init__(
        self,
        amide: str = "[NX3][CX3](=[OX1])[#6]",
        pi_ring: tuple[str, ...] = (
            "[a;r6]1:[a;r6]:[a;r6]:[a;r6]:[a;r6]:[a;r6]:1",
            "[a;r5]1:[a;r5]:[a;r5]:[a;r5]:[a;r5]:1",
        ),
        distance: float = 4.5,
        angle: "Angles" = (0, 30),
        new_angle: "Angles" = (0, 30),  # find a more descriptive name and parameters
    ) -> None:
        super().__init__(
            cation=amide,
            pi_ring=pi_ring,
            distance=distance,
            angle=angle,
        )
        self.new_angle = new_angle

    def detect(
        self, pi: "Residue", amide: "Residue",
    ) -> Iterator["InteractionMetadata"]:
        for metadata in super().detect(pi, amide):
            # do something with new_angle here
            if calculated_angle <= self.new_angle:
                metadata["new_angle"] = calculated_angle
                yield metadata

NHAr = ArHN.invert_role(
    "NHAr",
    "Interaction between a ligand (backbone amide) and residue (aromatic ring)",
)

Hopefully this answers your question!