$line =~ s/
    \*{2} ( [^\*]+ ) \*{2}
        \s
    ( kinase | isoform | protein | peptide | ligand )
        \s
    \${2} ( [^\$]+ ) \${2}
        \s
    [(,] \s
        \*{2} ( [^\*]+ ) \*{2}
    \s [),]
/**$1_$2_$3_($4)**/gx

##</code><code>##

sub delimited {
    my ( $delimiter ) = @_;
    my $qdelimiter = quotemeta $delimiter;
    return qr/ $qdelimiter{2} ( [^$qdelimiter]+ ) $qdelimiter{2} /x;
}

sub balanced {
    my ( $inside ) = @_;
    return qr/ [(,] $inside [),] /x;
}

my $stars = delimited '*';
my $dollars = delimited '$';
my $words = qr/( kinase | isoform | protein | peptide | ligand )/x;
my $parens = balanced qr/ \s $stars \s /x;

$line =~ s/ $stars \s $words \s $dollars \s $parens /**$1_$2_$3_($4)**/gx;